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THE  INTERNAL  SECRETIONS 
IN  PRACTICAL  MEDICINE 


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THE  INTERNAL  SECRETIONS 
IN  PRACTICAL  MEDICINE 


BY 

HENRY  R.  HARROWER,  M.  D. 

Fellow   of   the   Royal   Society   of  Medicine    (London) 

Sometime     Professor     of     Clinical    Diagnosis, 

Loyola   University,    Chicago;    Member 

American   Medical    Editors 

Association;   etc. 


CHICAGO 

CHICAGO  MEDICAL  BOOK  CO. 

1917 


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to  whom,  more  than  to  any  other  man,  practicing 
physicians  in  the  United  States  are  indebted  for 
painstaking  and  persistent  efforts  to  make  clear 
the  importance  of  the  glands  of  internal  secre- 
tion through  his  book,  "The  Internal  Secretions 
and  the  Principles  of  Medicine,"  and  his  numer- 
ous other  writings ;  and  for  directing  attention 
to  facts  concerning  the  functions  of  these  organs 
which,  though  long  discounted  by  some,  are  now 
increasingly  being  accepted  by  the   profession. 


Copyright  1917  by 
HENRY   R.    HARROWER,    M.    D. 


Printed   in   the   United   States  of   America 


TABLE  OF  CONTENTS 


J  Introduction :     Broadening    the    Scope    of    the 

Practice   of    Medicine.. 1 

II  The  Internal  Secretions  with  Special  Reference 

to  the  Treatment  of  Chronic  Disease 6 

III  The  Relation  of  the  Endocrine  Glands  to  Func- 

tional Disorders   16 

IV  The  Inconscpicuous,  Every-day  Forms  of  Thy- 

roid Insufficiency  30 

V  Pluriglandular  Insufficiency :  its  Incidence  and 

Treatment 43 

VI  Shell  Shock   (Neurasthenia)   and    the    Internal 

Secretions,    with    Suggestions    as    to    Treat- 
ment      62 

VII  The  Adrenal  Glands   and  their   Significance  in 

General   Practice 76 

VIII  The     Asthenias :      Myasthenia,     Neurasthenia, 

Chemasthenia  and  Psychasthenia — Endocrin- 
asthenia    91 

IX  The    Relation    of    the    Internal    Secretions    to 

Neruasthenia  in  Women 100 

X  Sex  Disabilities  Considered  as  Endocrine  Dys- 

crasias 114 

XI  The    Relation    of    the    Internal    Secretions    to 

Rheumatism  and  the  Rheumatic  Diathesis....  123 

XII  The  Relation  of  the  Thyroid  Gland  to  Epilepsy  136 

XIII  The  Defective  Child  from  the  Standpoint  of  the 

Internal   Secretions 148 

XIV  Organotherapy  in   Chronic   Disease  with   Spe- 

cial Reference  to  its  Possibilities  in  Cancer....  163 

XV  Some   Remarks   on   the   Treatment   of   Hyper- 

thyroidism   185 


viii  THE  INTERNAL  SECRETIONS 

XVI  The  Mamma  as  an  Internal  Secretory  Organ: 

Mammary  Therapeutics  196 

XVII  Connecting  Links  between  Endocrinology  and 

Oto-Rhinology    212 

XVIII  The  Treatment  of  Rickets 222 

XIX  The  Oral  Administration  of  Adrenalin 229 

XX  The  Adjunct  Treatment  of  Tuberculosis  with 

Certain  Organic   Extracts 237 


PREFACE 

A  NUMBER  of  physicians,  especially  those  who 
have  read  or  heard  one  or  more  of  my  papers  on 
subjects  related  to  the  glands  of  internal  secretion, 
have  expressed  a  desire  to  have  some  of  them  avail- 
able in  more  permanent  form.  Hence  this  collec- 
tion of  articles  in  book  form. 

Unlike  my  earlier  book,  "Practical  Hormone 
Therapy:  a  Manual  of  Organotherapy  for  Practi- 
tioners" (which  is  referred  to  occasionally  in  the 
following  pages),  the  units  comprising  this  col- 
lection were  not  written  originally  with  the  in- 
teniton  of  fitting  them  together  as  harmoni- 
ous and  consecutive  whole.  As  a  result  of  this 
there  is  a  certain  amount  of  redundancy  which  it 
has  seemed  best  to  leave  unmodified.  As  these  re- 
iterations have  been  reread  for  publication  in  this 
present  form,  the  fact  has  been  emphasized  that  no 
harm  can  come  from  reading  some  essential  more 
than  once,  especially  when  the  repetition  lends 
weight  to  some  particular  contention  in  one  paper 
and  to  a  different  one  in  another. 

Several  additional  paragraphs  have  been  added 
to  a  number  of  the  articles  as  originally  published 
in  the  medical  press,  with  the  idea  of  making  them 
more  comprehensive  and  as  up-to-date  as  possible. 
As  a  matter  of  fact  quite  a  number  of  experiences 
have  been  reported  in  current  literature  which  amp- 
lify my  position  in  a  previously  published  report, 


x  THE  INTERNAL  SECRETIONS 

and  their  inclusion  here  adds  emphasis  to  what  may 
have  been  said. 

No  attempt  has  been  made  to  cover  the  entire 
subject.  It  is  far  too  vast.  In  fact  it  would  take 
a  small  library  to  include  all  the  information  now 
at  our  disposal  regarding  the  glands  of  internal  se- 
cretion and  their  hormones.  However  some  time 
has  been  spent  in  preparing  a  fairly  complete  index 
so  as  to  facilitate  the  study  of  various  phases  of  the 
subjects  covered  which  may  be  of  immediate  inter- 
est to  the  reader  and  yet  be  discussed  in  more  than 
one  chapter  in  the  book. 

For  a  more  complete  consideration  of  the  thera- 
peutic side  of  this  subject  the  reader  is  referred  to 
my  book  mentioned  above;  and  also  to  a  quarterly 
journal  entitled  "ENDOCRINOLOGY"  which  is 
a  periodical  review  of  the  current  literature  on  all 
phases  of  this  subject.  This  journal  is  published 
by  the  Association  for  the  Study  of  the  Internal 
Secretions,  which  I  assisted  in  starting  in  1916. 
Further  information  regarding  the  activities  of  this 
Association  will  be  sent  to  any  interested  physician 
on  request. 

My  thanks  are  due  to  a  number  of  colleagues  for 
the  encouragement  given  me  to  have  these  papers 
collected  in  this  form,  as  well  as  to  the  publishers 
of  various  medical  journals  in  the  United  States 
and  Great  Britain  in  which  some  of  the  chapters 
already  have  appeared,  for  the  privilege  of  reprint- 
ing them  in  this  form. 


IN  PRACTICAL  MEDICINE  he 

I  realize  that  some  of  my  statements  are  open  to 
criticism,  and  I  will  welcome  any  constructive  criti- 
cal remarks  or  queries.  I  do  not  profess  to  be  more 
than  an  ardent  student  of  what  is  to  me  a  very  fas- 
cinating subject. 

I  need  not  apologize  for  my  interest  in  this  sub- 
ject, nor  for  the  enthusiasm  it  has  engendered.  I 
only  hope  that  some  hint  in  this  book  may  serve  to 
make  a  real  difference  to  some  reader's  considera- 
tion of  a  difficult  case;  and  that  as  a  result  of  read- 
ing it  some  tangible  advantage  may  accrue  to  both 
patient  and  physician. 

HENRY  R.  HARROWER. 
Glendale,  California. 
July,  1917. 


THE  INTERNAL  SECRETIONS 
IN  PRACTICAL  MEDICINE 


i 

INTRODUCTION: 

BROADENING  THE  SCOPE  OF  THE 
PRACTICE  OF  MEDICINE 

AS  our  knowledge  of  physiology  becomes  more 
intimate  and  our  application  of  some  of  the  ideas 
set  forth  by  the  experimentalists  are  put  into  prac- 
tice, we  find  the  scope  of  medical  practice  broad- 
ening in  a  remarkable  manner.  Revolution  follows 
revolution  until  the  standardized  procedures  of  to- 
day differ  as  radically  from  those  of,  say,  25  years 
ago  as  do  the  present  conceptions  of  the  physio- 
logic relations  of  the  various  parts  of  the  body  com- 
pared with  those  held  at  that  time. 

Undoubtedly  the  most  radical  as  well  as  impor- 
tant advance  in  medicine  is  our  better  knowledge 
of  the  endocrine  system — that  interlocking,  though 
widely  separated,  collection  of  glands  of  internal 
secretion  which  we  now  know  is  in  supreme  con- 
trol of  growth,  both  physical  and  mental;  metabo- 
lism; the  sympathetic  nervous  system,  with  its  reg- 
ulation of  vascular  tone  and  blood  pressure;  as  well 

(1) 


2  THE  INTERNAL  SECRETIONS 

as  the  indefinite  and  complex  factors  gathered  to- 
gether into  the  one  well-known  term  "constitu- 
tion." The  hormones  produced  by  these  wonder- 
ful glands  are  secreted  into  the  blood  and  serve  to 
correlate  function  and  harmonize  many  of  the 
widely  differing  functions  of  the  body.  Their 
chemical  messages  are  of  such  a  nature  that  to  ig- 
nore them  and  their  subtle  influence  is  to  miss  a 
very  large  and  important  part  of  the  information 
which  may  be  at  the  disposal  of  any  observant  phy- 
sician. 

Just  as  the  discovery  of  the  hormones  and  the  un- 
ravelling of  the  intricate  skein  of  their  relationships 
has  revolutionized  physiology,  so  the  knowledge 
we  have  been  able  to  deduce  from  these  facts  is 
revolutionizing  therapeutics,  for  it  is  now  generally 
recognized  that  organotherapy  is  making  possible 
the  successful  treatment  of  many  chronic  and  com- 
plicated disorders. 

The  study  of  these  endocrine  glands  will  well  re- 
pay the  interested  reader  of  the  hundred  and  one 
articles  and  abstracts  now  appearing  in  current 
medical  literature;  and  as  he  applies  the  obvious 
treatment  in  a  given  case,  he  will  be  both  surprised 
and  pleased  at  the  results  which  so  often  follow 
the  application  of  this  altogether  scientific  and  rea- 
sonable branch  of  therapy. 

It  is  not  necessary  within  the  limits  of  this  brief 
introduction  to  do  more  than  direct  attention  to 


IN  PRACTICAL  MEDICINE  3 

the  great  possibilities  of  this  phase  of  medicine; 
and  to  outline  the  essential  facts  upon  which  the 
science  of  practical  hormone  therapy  has  been 
built. 

By  far  the  greatest  principle  is  that  of  "homo- 
stimulation,"  which  is  included  in  what  has  come 
to  be  known  as  Hallion's  law,  which  is  as  follows: 
"Extracts  of  an  organ  exert  on  the  same  organ  an 
exciting  influence  which  lasts  for  a  longer  or 
shorter  time.  When  the  organ  is  insufficient  it  is 
conceivable  that  this  influence  augments  its  action 
and,  when  it  is  injured,  that  it  favors  its  restora- 
tion." This  has  been  demonstrated  experimentally 
and  clinically  so  many  times,  that  it  is  almost  axi- 
omatic, though  it  is  not  infallible,  and  may  still  be 
criticized  occasionally  by  some.  Granting  what 
Hallion  has  said,  functional  insufficiencies  of  many 
of  these  organs  may  be  expected  to  be  favorably 
influenced  by  giving  suitable  doses  of  the  corre- 
sponding gland  secured  from  animals. 

Closely  allied  to  this  is  another  slightly  different 
phase  of  organotherapy.  Frequently  it  is  not  suf- 
ficient to  attempt  to  stimulate  a  lagging  gland.  One 
must  replace,  in  part  at  least,  the  missing  substance 
that  it  should  have  been  furnishing  to  the  body. 
This  is  what  is  known  as  "substitutive  organother- 
apy." In  conditions  like  cretinism  or  infantilism 
where  the  thyroid  or  gonads  are  absent,  one  can 
measurably  restore  the  activity  that  is  reduced  or 
absent  because  of  the  lack  of  the  hormone  stimuli 


4  THE  INTERNAL  SECRETIONS 

from  the  glands  in  question.  In  severe  functional 
conditions  we  expect  to  benefit  from  organother- 
apy in  at  least  two  ways — by  substituting  for  the 
missing  hormones  and,  also,  by  causing  what  is 
known  as  homostimulation,  the  principle  so  well 
described  in  Hallion's  law  just  quoted. 

Again  the  chemical  substances  produced  in  the 
normal  physiologic  action  of  certain  of  the  duct- 
less glands  have  a  definite  pharmacological  action 
and  its  application  in  medicine  is  the  so-called 
"specific  organotherapy,"  for  the  influence  of  the 
drug — these  extracts  must  be  considered  purely  as 
drugs — favors  some  desirable  action  as,  for  in- 
stance, the  stimulation  of  the  uterus  with  the  pos- 
terior pituitary  principle  during  a  delayed  labor. 
In  such  a  case  there  is  no  evidence  whatever  to 
prove  that  this  hormone  principle  is  absent  or  even 
that  the  pituitary  is  not  working  normally.  We 
simply  make  use  of  the  specific  action  of  this  sub- 
stance. 

Finally  in  our  clinical  and  laboratory  experi- 
menal  work  we  have  found  that  the  administration 
of  certain  "extracts"  (as  they  are  usually  but,  in 
some  instances,  erroneously,  called)  cause  certain 
physiologic  reactions  and  we  make  use  of  these 
facts  by  applying  what  is,  strictly  speaking,  "em- 
pirical organotherapy." 

No  matter  in  what  conditions  organotherapy 
may  be  used,  irrespective  of  its  "scientific"  or  its 
"empirical"  basis,  it  is  a  valuable  addition  to  our 


IN  PRACTICAL  MEDICINE  5 

medical  armamentarium,  for  where  its  application 
is  physiologically  proper  one  may  expect  it  to  give 
results  and  therefore  be  rational,  while  in  the  not 
infrequent  cases  where  there  may  be  a  question 
about  the  the  exact  raison  d'etre  of  a  certain  or- 
ganotherapeutic  remedy,  it  is  rational  because  it  is 
resultful.  "We  care  not  how  the  results  come,  pro- 
vided they  come,  and  come  quickly." 

Organotherapy,  however,  is  only  a  small  part  of 
endocrinology;  a  part  of  it  which  has  not  yet  recov- 
ered from  the  rank  empiricism  and  quackery  of  a 
few  decades  ago.  The  study  of  the  relations  of  the 
glands  of  internal  secretion  whether  followed  by 
the  application  of  organotherapeutic  procedures  or 
not,  is  of  great  importance;  and  as  various  phases 
are  considered  from  certain  practical  points  of 
view,  it  will  be  clear  that  the  remark  of  one  writer 
— "in  these  days  the  internal  secretions  are  being 
studied  as  never  before,  and  most  assuredly  are 
coming  into  their  own" — is  perfectly  true;  and  that 
there  is  plenty  of  excuse  for  the  widespread  interest 
now  being  accorded  to  this  growing  branch  of 
medicine. 

The  more  time  and  attention  that  is  given  to  the 
practical  study  of  endocrinology,  the  broader  will 
be  the  scope  of  the  practice  of  medicine  and  the 
greater  the  professional  prestige  and  profit  of  the 
aggressive  physician  who  measures  and  applies  the 
advances  in  medicine  by  the  only  reasonable  stand- 
ard— the  standard  of  "tests-and-results." 


II 

THE  INTERNAL  SECRETIONS  WITH  SPE- 
CIAL REFERENCE  TO  THE  TREAT- 
MENT OF  CHRONIC  DISEASE 

THE  rapidly  increasing  fund  of  information 
which  students  of  endocrinology  are  making  avail- 
able for  interested  members  of  the  profession,  is 
modifying  many  of  our  conceptions  of  internal 
medicine  as  well  as  changing  some  of  our  ideas  re- 
garding treatment. 

As  we  bring  these  facts  to  bear  upon  numerous 
and  widely  differing  phases  of  medical  practice,  it 
soon  becomes  clear  that  a  great  fundamental  prin- 
ciple is  involved,  which  neither  the  skepticism  of 
the  ignorant  nor  the  passage  of  time  can  change. 
The  hormones,  or  active  principles  elaborated  by 
the  glands  of  internal  secretion,  exert  a  decided  in- 
fluence upon  those  factors  concerned  in  the  causa- 
tion as  well  as  the  cure  of  the  majority  of  chronic 
diseases.  Hence,  hormone  therapy,  or  the  use  of 
animal  extracts  in  therapeutics,  contains  potentiali- 
ties worthy  of  practical  consideration  by  those  who 
treat  the  numerous  persistent  and  intractable  ills 
which  the  flesh  seems  to  be  inheriting  in  increasing- 
degree. 


An  address  read  before  the  Southern  California  Medical  So- 
ciety at  Los  Angeles,  California,  December  2nd,  1915. 

(6) 


IN  PRACTICAL  MEDICINE  7 

The  subject  is  still  in  its  formative  stage,  and 
occasionally  one  finds  those  who  look  at  it  askance, 
despite  the  innumerable  encouragements  which  we 
are  constantly  meeting  from  day  to  day.  I  just 
happened  to  pick  up  the  current  issue  of  the  Ameri- 
can Journal  of  Obstetrics  (Nov.,  1915,  p.  885),  and 
read  an  interesting  discussion  on  the  value  of  cor- 
pus luteum  therapy.  One  of  the  participants,  Dr. 
A.  T.  Jones,  of  Providence,  made  a  statement  which 
I  would  like  to  repeat :  "With  reference  to  organo- 
therapy, I  think  the  profession  is  divided  into  two 
classes.  As  a  rule  one  class  loses  its  head  over  or- 
ganotherapy and  believes  everything  can  be  cured 
by  organic  extracts" — and,  by  the  way,  I  have  been 
put  into  this  class  because  my  recent  book,  "Prac- 
tical Hormone  Therapy,"  merely  for  the  sake  of 
comprehensiveness,  takes  up  some  forms  of  organo- 
therapy with  which  I  have  no  experience,  because 
I  have  little  faith  in  them — "while  the  other  class 
is  that  group  who  would  not  give  organic  extracts 
even  if  they  knew  they  were  going  to  get  a  good 
result.  They  will  not  take  it  up;  they  never  have 
tried  it.  I  believe  these  extracts  are  of  value,  and 
particularly  the  corpus  luteum  extract." 

The  writer  fully  agrees  with  Dr.  Jones,  and  while 
one  meets  more  men  who  should  be  in  the  second 
as  compared  with  the  first  class,  I  am  finding  an  in- 
creasing number  of  progressive  physicians  who  are 
open  to  conviction  and  who,  realizing  the  vast  pos- 
sibilities of  this  study,  are  exploring  its  depths  and 


8  THE  INTERNAL  SECRETIONS 

finding  many  most  pleasing  experiences  there.  In 
the  same  discussion  just  referred  to,  Leighton,  in 
concluding,  said:  "This  therapy  has  its  limitations. 
It  is  not  a  cure-all.  There  is  one  trouble,  and  that 
is  we  do  not  use  it  enough !"  And  this  applies  in 
other  equally  practical  phases  of  the  subject  to 
which  brief  allusion  shortly  will  be  made. 

With  very  few  exceptions,  all  chronic  diseases 
have  associated  with  them,  and  are  aggravated  by, 
a  disturbance  in  one  or  more  of  the  internal  secre- 
tory organs.  If  this  position  is  correct,  we  have 
another  angle  from  which  to  consider  those  of  our 
patients  who  are  chronic  sufferers.  Many  articles 
and  editorials  in  our  own  and  foreign  medical  lit- 
erature (and,  parenthetically,  it  must  be  admitted 
that  abroad  they  do  more  work  in  this  line,  hence 
more  information  is  to  be  found  in  the  French, 
Italian  and  English  literature)  direct  attention  to 
the  new  avenues  of  therapeutic  endeavor  that  are 
being  opened  up.  And  they  are  being  well  trav- 
eled. Organotherapy  is  being  studied  as  never  be- 
fore, and  those  who  are  attracted  by  its  fascina- 
tions, are  learning  that  the  results  sometimes  at- 
tained are  not  simply  good,  but  wonderful. 

You  all  have  personal  knowledge  of  the  diverse 
therapeutic  possibilities  of  the  principle  from  the 
infundibulum  of  the  pituitary  body  first  suggested 
as  a  remedy  by  Blair  Bell,  of  Liverpool,  as  late  as 
1909.  You  know  of  its  startling  effects  upon  the 
uterus  in  labor  and  of  its  value  as  a  postpartum 


IN  PRACTICAL  MEDICINE  9 

remedy,  its  influence  in  such  remote  conditions  as 
intestinal  paresis,  anuria  and  agalactia;  and  finally 
of  its  definite  value  as  a  heart  tonic.  In  fact  in  a 
personal  letter  from  the  late  Sir  Lauder  Brunton, 
he  remarked  that  pituitrin  was  a  more  efficient 
heart  stimulant  than  either  digitalis  or  strychnia, 
and  it  is  none  too  often  used  for  this  purpose  either. 
Now  I  have  not  enumerated  all  the  advantages  of 
this  single  remedy  and  there  are  other  organo- 
therapeutic  preparations  almost  as  wonderful. 

None  the  less  to  some  "it  is  still  too  early  to  pass 
judgment,"  and  as  another  put  it,  "we  are  still 
groping  in  the  very  dimly  lighted  recesses  of  this 
new  study."  However,  it  is  encouraging  to  recall 
that  a  single  experience  is  worth  ten  times  as  much 
as  an  argument;  and  the  tests-and-results  method 
is  the  only  way  to  convince  one's  self  that  what 
may  be  said  here  to-night  is  not  just  the  dream  of 
a  visionary  crank. 

Obviously  we  cannot  more  than  refer  to  the  mere 
fundamentals  involved  in  the  relation  of  the  in- 
ternal secretions  to  the  incidence  and  control  of 
chronic  disease.  We  can,  however,  refresh  our 
minds  on  a  few  of  the  better  known  matters  and, 
perhaps,  hint  briefly  of  some  of  the  other  possibili- 
ties of  this  rapidly  advancing  and  increasingly  in- 
teresting subject. 

Probably  more  has  been  written  about  the  thy- 
roid than  about  any  of  the  other  glands  of  internal 
secretion.     It  has  been  most  carefully  studied  for 


10  THE  INTERNAL  SECRETIONS 

many  years  and  its  pathology  and  physiology  are 
only  just  beginning  to  be  fairly  well  understood; 
in  fact,  though  this  is  probably  the  best  known  of 
the  endocrine  glands,  we  are  not  yet  able  to  isolate 
its  active  principles,*  and  we  have  still  much  to 
learn  of  the  intricacies  of  its  physiologic  relations. 
The  epoch-making  work  of  George  Murray,  now 
of  Manchester,  in  the  original  application  of  thy- 
roid therapy  in  the  major  thyroid  disorders  myxe- 
dema and  cretinism,  seems  to  have  directed  atten- 
tion far  beyond  the  much  more  common  minor  thy- 
roid insufficiencies,  and  evidence  of  this  is  found 
in  the  last  U.  S.  P.,  for  in  it  the  dosage  of  desiccated 
thyroids  is  given  as  5  grains,  an  altogether  pre- 
posterous dose  in  the  majority  of  the  conditions  in 
which  thyroid  is  now  used.  Instead  of  this  pharma- 
copceial  dose,  which,  by  the  way,  may  be  quite  rea- 
sonable in  certain  cases  of  athyroidia  and  severe 
thyroid  disorders,  we  now  rarely  use  more  than  one 
grain  and  frequently  a  quarter  or  half  a  grain  three 
times  a  day  is  quite  sufficient  to  bring  about  very 
satisfactory  results. 

The  thyroid  gland  is  functionally  disturbed, 
slightly  in  some  cases,  more  in  others,  in  many 
every-day  conditions,  many  of  which  are  chronic 
in  their  manifestations.  Those  disorders  which  are 
dependent  upon  perversions   of   the   metabolism — 


*Since  this  was  written  a  communication  from  the  Mayo 
Clinic  by  E.  C.  Kendall  announces  the  discovery  there  of  what  ap- 
pears to  be  the  active  principle  of  the  thyroid  gland. 


IN  PRACTICAL  MEDICINE  11 

rheumatism,  gout  and  perhaps,  in  some  degree,  dia- 
betes— usually  have  a  thyroid  element  of  greater  or 
less  importance.  Following  the  original  work  of 
my  very  good  friend,  Dr.  Eugene  Hertoghe,  of 
Antwerp,  Leopold  Levi  and  his  associate,  Baron 
Henri  de  Rothschild,  of  Paris,  have  made  a  most 
minute  study  of  the  part  that  the  thyroid  plays  in 
almost  every  disorder.  Every  patient  who  comes 
to  their  hospital  virtually  is  studied  as  a  thyroid 
case,  and  in  their  recent  book,  "La  Petite  Insuffi- 
sance  Thyroidienne  et  son  Traitement,"  it  is  re- 
markable to  note  how  large  a  variety  of  conditions 
have  a  distinct  thyroid  aspect  and,  more  practical 
yet,  are  either  directly  benefited  by  the  administra- 
tion of  thyroid  or  the  regular  treatment  is  made 
more  effective  by  the  addition  of  one  or  two  centi- 
grammes of  thyroid  per  day.  More  than  forty  dis- 
orders are  in  this  category  from  neurasthenia  to 
psoriasis.  Yet,  like  most  enthusiasts,  they  have 
been  laughed  at,  and  sneered  at,  too,  for  fifteen 
years  or  more.  Still  Levi  and  de  Rothschild  have 
mastered  the  technique  of  thyroid  medication  and 
use  it  with  much  advantage  in  many  conditions, 
both  distinctly  thyroid  in  origin  and  in  which  no 
obvious  thyroid  disturbance  can  be  found.  In  this 
country  we  have  still  a  few  things  to  learn  in  this 
particular  corner  of  this  field. 

Closely  related  to  thyroid  hypofunction  is  the 
condition  known  as  pluriglandular  insufficiency,  an 
extremely    common    symptom    complex   which    is 


12  THE  INTERNAL  SECRETIONS 

more  than  occasionally  overlooked.  The  statement 
recently  has  been  made  that  disorders  of  the  hor- 
mone-bearing organs  always  affect  more  than  one 
gland,  since  the  intimacy  of  these  organs  renders  it 
impossible  for  one  gland  to  be  disturbed  without  an 
associated  disturbance  in  one  or  more  of  the  others 
related  to  it.  There  are  two  principal  forms  of 
pluriglandular  insufficiency,  the  organic  and  the 
functional.  The  former  commonly  asserts  itself  in 
certain  developmental  disorders  and  in  syphilis. 
Right  here  is  a  phase  of  syphilology  which  deserves 
cloesr  attention.  In  a  paper  which  I  prepared  for 
a  special  issue  of  The  Practitioner  (London),  on 
Pluriglandular  Insufficiency,*  a  number  of  reports 
were  collated  showing  the  relation  of  syphilis  to 
ductless  glandular  syndromes.  In  such  cases  the 
information  has  usually  been  elicited  at  the  autopsy 
table,  though  several  cases  of  obvious  endocrine 
disorder  were  traced  to  syphilis  and  treated  with 
comparative  satisfaction.  The  chief  deduction  that 
may  be  made  from  this  is  that  syphilis  as  a  general- 
ized disease,  may  and  does  affect  the  hormone 
producing  system  and  its  treatment  may  be  ex- 
tended by  adding  to  the  usual  arsenic  or  mercury 
treatment,  suitable  organotherapeutic  extracts  to 
stimulate  the  various  semi-active  ductless  glands 
and  thus  cause  a  general  betterment  not  otherwise 
attained. 

In  this  connection  an  abstract  in  the  Tournal  of 


♦Chapter  V  of  this  book. 


IN  PRACTICAL  MEDICINE  13 

the  American  Medical  Association  (October  2, 
1915,  p.  1223),  is  instructive.  "A  striking  case  is 
reported  by  Korczynski  in  which  inherited  syphilis 
seems  to  have  impaired  the  functioning  of  the  thy- 
roid, hypophysis,  ovaries  and  blood-producing  or- 
gans. The  child  was  mentally  backward.  Thyroid 
treatment  and  treatment  for  syphilis  were  given  to- 
gether, and  a  pronounced  change  for  the  better  was 
soon  apparent  and  has  continued  to  progress.  .  .  ." 
The  functional  forms  of  pluriglandular  insuffi- 
ciency are  not  associated  with  the  obvious  mani- 
festations that  the  more  marked  organic  conditions 
usually  show.  The  reduced  production  of  the 
"chemical  messengers"  is  none  the  less  present,  for 
when  an  individual  is  run-down,  for  instance,  when 
the  elimination  is  not  as  it  should  be,  when  the 
muscles  are  easily  fatigued,  the  nerves  easily  ex- 
cited and  there  are  present  the  other  usual  manifes- 
tations of  neurasthenia  and  debility,  one  can  hardly 
believe  that  the  glands  of  internal  secretion  alone 
are  working  normally.  In  such  cases  pluriglandu- 
lar therapy  is  an  exceptionally  useful  treatment, 
alone  or  combined  with  other  treatment  which  the 
exigencies  of  the  case  may  indicate.  It  may  be 
well,  incidentally,  to  remark  that  in  ovarian  dis- 
orders where  luteal  therapy  is  indicated  and  likely 
to  be  effective,  the  addition  of  some  of  the  extracts 
of  glands  known  to  be  intimately  related  to  the 
gonads,  the  thyroid  and  the  pituitary,  will  more 


14  THE  INTERNAL  SECRETIONS 

than  likely  make  the  response  to  treatment  more 
decided  and  resultful. 

The  control  of  the  sympathetic  nervous  system 
by  the  chromaffin  hormone  produced  in  the  medul- 
lary portion  of  the  adrenal  glands,  makes  these  or- 
gans of  supreme  importance  in  numerous  condi- 
tions. Take  that  most  common  of  all  clinical  mani- 
festations, pain,  and  recall  that  it  has  been  shown 
by  competent  investigators  to  be  a  decided  stimu- 
lant to  the  adrenals  and  thus  "wears  them  out." 
This  is  a  partial  explanation,  at  least,  of  the 
clinical  value  of  preparations  of  this  character  in 
many  disorders  including  cholera  (with  its  extreme 
pain  and  collapse),  shock  (with  its  associated  acute 
adrenal  insufficiency  first  intelligently  discussed  by 
Sajous,  of  Philadelphia  about  13  years  ago),  post- 
febrile collapse  or  asthenia  (conditions  definitely 
traced  to  hypoadrenia  and  just  as  definitely  bene- 
fited by  the  obvious  therapeutic  procedure — the  ad- 
ministration of  adrenalin  or  similar  products),  and 
other  important  disorders. 

Crile's  valuable  studies  which  have  given  us 
anoci-association  and  the  power  to  reduce  or  en- 
tirely eliminate  post-anesthetic  shock  by  removing 
the  stimuli  which  unduly  overwork  the  kinetic  sys- 
tem, are  based  in  a  large  measure  upon  the  physio- 
logical chemistry  of  the  adrenal  medulla,  and  while 
his  most  profitable  work  has  been  of  a  prophylactic 
nature — to  prevent  the  unpleasant  results  at  one 
time    not    infrequently    following    operations,  the 


IN  PRACTICAL  MEDICINE  15 

same  principle  applies  in  therapeutics,  for  when  the 
adrenals  have  been  depleted  and  the  body  is  suffer- 
ing from  the  lack  of  the  normal  amount  of  adrenin, 
with  low  blood  pressure,  asthenia  and  collapse,  the 
natural  thing  to  do  is  to  secure  the  missing  sub- 
stance from  animals  and  give  it  as  quickly  and  di- 
rectly as  possible,  just  as  we  have  learned  to  do  the 
same  thing  with  thyroids  from  sheep  or  corpora 
lutea  from  sows. 

Now  you  realize,  of  course,  that  this  subject 
which  was  chosen  on  the  spur  of  the  moment  as 
the  result  of  a  telegraphic  request  by  your  Secre- 
tary to  my  friend,  Col.  McCullough,  of  the  Sur- 
geon-General's Library  in  Washington,  has  been 
considered  only  in  its  broadest  general  aspects.  It 
is  as  broad  as  the  influence  of  the  hormones  upon 
physiology,  and  the  limits  of  its  practical  useful- 
ness have  not  yet  been  reached,  although  we  have 
already  learned  many,  many  things. 

There  is  much  more,  and  the  more  we  study  and 
apply  these  principles  in  our  work,  and  especially 
that  part  of  it  which  concerns  the  treatment  of 
chronic  disorders,  the  more  we  appreciate  the  en- 
thusiasm of  many  who  are  daily  delving  into  these 
secrets  and  are  finding  in  them  so  much  that  is 
available  in  the  every-day  routine  of  medicine. 


Ill 

THE     RELATION     OF    THE     ENDOCRINE 
GLANDS  TO  FUNCTIONAL  DISORDERS 

WHILE  the  study  of  the  glands  of  internal  se- 
cretion has  reecived  a  great  impetus  in  the  past  few 
years,  and  the  science  underlying  the  diagnosis  and 
treatment  of  endocrine  disorders  certainly  has  ad- 
vanced greatly  in  this  period,  there  is  still  a  well- 
defined  tendency  to  consider  ductless  glandular  dis- 
ease per  se  rather  than  the  functional  pathology 
resulting  from  modifications  in  the  chemical  activ- 
ities of  these  glands. 

Disorders  of  function  obviously  are  of  far  greater 
clinical  importance  than  organic  disease  not  merely 
because  of  their  much  greater  frequency,  but  be- 
cause the  former  are  merely  more  or  less  slight 
aberrations  from  the  average,  whereas  the  latter 
involve  structural  changes  which  in  many  cases  are 
only  partially  amenable  to  the  very  best  of  treat- 
ment. 

The  discovery  of  cretinism,  myxedema,  the  Ad- 
dison, Froehlich  or  Graves  syndromes  is  compara- 
tively easy,  for  each  of  these  conditions  is  a  dis- 
ease with  a  more  or  less  definite  pathology  and 
symptomatology.     But  the  insidiousness  of  func- 


Read  in  a  Symposium  on  Functional  Pathology  before  the 
Sections  on  Medicine  and  Neurology,  California  State  Medical  So- 
ciety at  Coronado,  April,  1917. 

(16) 


IN  PRACTICAL  MEDICINE  17 

tional  pathology  of  the  glands  of  internal  secretion 
and  the  frequency  with  which  disturbances  of  their 
functions  play  a  part  in  many  acute  as  well  as 
chronic  conditions  of  every  day  occurrence,  makes 
their  study  of  greater  clinical  importance  than  the 
more  definite  and  easier  demonstrated  ductless 
glandular  diseases  of  which  a  few  have  just  been 
enumerated. 

With  our  added  knowledge  of  the  physiology  of 
the  endocrine  glands  and  its  importance,  we  are 
enabled  to  study  many  a  functional  condition  from 
a  viewpoint  which  is  considerably  different  from 
that  of  past  years,  and  this  may  enable  us  so  to 
modify  our  treatment  that  many  of  the  hitherto 
intractable  disorders  may  now  respond  to  our 
efforts. 

In  an  editorial  in  the  New  York  Medical  Jour- 
nal (1)  published  a  few  months  ago,  the  importance 
of  functional  medicine  was  emphasized  and  it  was 
remarked  that  in  order  that  the  advances  in  the 
pathological  sciences  might  be  fully  appreciated 
and  be  of  the  greatest  usefulness  "there  is  need 
for  a  better  understanding  of  fundamental  physio- 
logical principles  and  a  much  wider  appreciation 
of  functional  possibilities.  To  this  must  be  added 
the  ability  to  correlate  new  findings  and  to  detect 
departures  from  the  normal  in  their  early  stages.  It 
is  only  from  such  studies  as  these  that  we  may  hope 
to  acquire  that  breadth  and  keenness  of  vision  so 
essential  to-day  to  offset  the  narrowness  and  con- 


18  THE  INTERNAL  SECRETIONS 

centration  of  specialism. "  As  a  result  of  this,  in 
the  words  of  the  same  editorial  writer  just  referred 
to,  "our  diagnoses  will  become  more  fundamental 
and  our  therapeutics  more  vital." 

I  have  seen  many  a  case  with  the  diagnosis  of 
rheumatism  or  tuberculosis  or  neurasthenia  or  in- 
digestion in  which  the  ductless  glandular  element 
was  not  even  thought  of.  Why  should  a  physician 
study  the  thyroid  activity  of  a  patient  with  tubercu- 
losis, or  connect  the  adrenals  with  neurosis?  As  a 
matter  of  fact,  it  is  impossible  for  a  severe  infection 
like  rheumatism  or  a  protracted  disease  like  tuber- 
culosis not  to  make  a  very  decided  mark  upon  one 
or  more  of  the  glands  of  internal  secretion,  and 
since  these  glands  respond  so  easily  to  the  influence 
of  infections,  toxemias  or  even  psychological 
states,  it  takes  but  a  short  time  to  involve  them. 

It  can  be  taken  for  granted  that  questions  con- 
cerning therapeutics  always  must  be  matters  of 
opinion  in  which  unanimity  is  unlikely;  but  ques- 
tions of  pathologic  physiology  are  now  being  ascer- 
tained with  precision  and  the  subject  is  being  put 
upon  such  a  basis  that  dissent  is  not  so  probable. 
At  least  the  relations  of  certain  functions  of  the 
body  are  now  sufficiently  understood  so  that  we 
can  refer  to  them  with  confidence  and  it  is  to  some 
of  these  that  I  wish  to  direct  your  attention  to-day. 

Every  function  of  the  body  is  in  some  way  di- 
rectly or  remotely  connected  with  the  work  of  the 
endocrine  glands,  hence  disorder  in  them  invari- 


IN  PRACTICAL  MEDICINE  19 

ably,  let  me  emphasize  this  word,  spells  disorder  in 
other  functions.  So  really  the  functional  pathology 
of  the  endocrine  glands  is  reflected  in  almost  every 
phase  of  the  practice  of  medicine,  for  growth, 
metabolism,  oxidation,  resistance  to  infection  and 
the  more  indefinable  but  none  the  less  important 
fundamentals,  constitution  and  temperament,  are 
now  considered  to  be  dependent  upon  ductless 
glandular  action. 

Furthermore  the  clinical  leading  of  information 
of  this  character  prompts  us  to  use  measures  in  the 
place  of  or  in  conjunction  with  those  to  which  we 
have  become  accustomed,  and  such  modifications 
of  the  treatment  are  a  decided  advantage  towards 
greater  success.  In  other  words,  when  we  are  con- 
sidering a  given  disease  we  will  find  out  more  of 
value  and  be  able  to  render  a  more  satisfactory 
service  if  the  functional  pathology  of  the  endocrine 
organs  is  also  considered — if  we  consider  the  pa- 
tient as  a  whole  rather  than  his  disease  as  a  unit. 
As  yet,  however,  this  is  not  the  rule,  for  there  still 
seems  to  be  a  tendency  to  study  diseases  instead 
of  patients,  and  to  treat  certain  text-book  symp- 
toms with  whatever  measures  may  be  uppermost 
in  the  physician's  mind. 

Our  knowledge  of  clinical  endocrinology  might 
be  considerably  better,  at  least  in  so  far  as  discern- 
ing the  earliest  beginnings  of  these  subtle  influ- 
ences is  concerned.  It  is  not  in  the  discovery  of 
well-differentiated  disorder,  but  in  the  appreciation 


20  THE  INTERNAL  SECRETIONS 

of  the  ordinary  chemical  changes  of  the  beginnings 
of  disease — the  early  steps  in  functional  pathologi- 
cal change — that  one  attains  the  best  results  and 
the  greatest  personal  satisfaction. 

In  an  editorial  note  on  cancer,  Clinical  Medi- 
cine (2)  remarks:  "We  still  are  in  constant  pro- 
test against  the  neglect  of  the  study  of  physiology 
now  prevalent  in  the  entire  profession.  Over  and 
over  again  we  have  urged  upon  the  profession  the 
importance  of  so  studying  the  physiology  of  the 
human  body  that  the  very  first  departure  from  nor- 
mal activity  of  any  of  the  functions  shall  be  de- 
tected and  the  cause  of  such  departure  removed.  .  .  . 
To  the  chemistry  of  the  blood,  we  must  look  for  the 
essential  cause  of  cancer.'' 

Physiology  is  too  complex  for  internal  medicine, 
much  less  the  other  branches  of  medicine,  to  be  re- 
duced to  one  single  phase  of  study.  The  broader 
our  conceptions  of  the  physiologic  functions  of  the 
body,  the  more  intimate  is  our  knowledge  of  the 
cellular  interrelationships  of  the  various  integral 
parts  of  the  organism;  and  hence  the  greater  is  our 
appreciation  of  the  importance  of  more  or  less  in- 
significant modifications  of  these  relationships — or 
"functional  pathology"  as  it  is  called. 

Since  we  have  begun  comparatively  recently  to 
realize  the  comprehensiveness  of  the  so-called 
"hormone  balance,"  we  have  also  naturally  had  our 
eyes  opened  to  the  importance  of  aberrations  in 
one  or  more  of  the  elements  which  go  to  maintain 


IN  PRACTICAL  MEDICINE  21 

this  balance;  and  disordered  function,  be  it  ever  so 
slight,  now  frequently  directs  attention  to  an  in- 
significant thyroid,  pituitary  or  other  endocrine 
complex  which  until  very  recently  invariably  was 
overlooked. 

It  may  not  be  possible  to  substantiate  this  posi- 
tion in  the  mind  of  every  skeptic  in  the  brief  time 
allotted;  but  we  might  take  up,  say,  half  a  dozen 
constitutional  diseases  such  as  we  have  to  meet 
every  day,  and  reiterate  some  opinions  which  seem 
to  establish  that  the  endocrine  element  in  these  is 
prominent  (in  varying  degree  depending  upon  the 
physiological  substratum  of  the  individual  and 
their  reactivity  to  the  fundamental  causes  of  dis- 
ease) and,  therefore,  of  no  mean  clinical  im- 
portance. 

I  propose  to  refer  to  rheumatism,  epilepsy,  neu- 
rasthenia, diabetes,  tuberculosis  and  syphilis;  and 
though  each  is  a  subject  worthy  of  a  comprehens- 
ive discussion,  I  will  gather  together  some  hints 
which  I  hope  may  remain  with  you  after  this  meet- 
ing is  over: 

Rheumatism  is  "a  constitutional  disease  with  lo- 
cal manifestations."  Some  say  that  it  is  due  to  an 
infection,  others  to  uric  acid,  still  others  to  acid- 
osis. Each  may  be  correct,  for  there  are  almost  as 
many  forms  of  rheumatism  as  there  are  rheumatic 
patients.  If  it  is  an  infection  with  the  s.  rheumat- 
icus  or  other  microorganism,  the  thyroid,  as  an  im- 
portant part  of  "the  powers  of  resistance"  of  the 


22  THE  INTERNAL  SECRETIONS 

body,  is  concerned.  If  it  is  a  toxemia  the  adrenals 
must  be  influenced  in  some  way,  for  of  all  the  or- 
gans in  the  body,  endocrine  or  otherwise,  the  ad- 
renals are  the  most  susceptible  to  toxins — they  re- 
act on  the  slightest  provocation,  and  are  largely  re- 
sponsible for  the  well-known  sympathetic  mani- 
festations of  toxemia. 

The  thyroid  is  more  often  implicated  than  any 
other  endocrine  organ,  and  subthyroidism  many 
times  is  the  one  and  only  cause  of  what  is  supposed 
to  be  rheumatism.  The  sluggish  metabolism  of  the 
rheumatic  is  so  nearly  like  that  of  the  cretin  or 
myxedematous  patient  (and  responds  equally  to 
indicated  treatment)  that  I  believe  the  French 
(Gauthier,  Gilbert,  Carnot  and  Leopold  Levi)  are 
right  in  emphasizing  thyroid  dyscrasia  as  an  actual 
cause  of  "rheumatism."  (3) 

As  one  acquires  the  habit  of  considering  rheuma- 
tism from  this  angle,  it  is  surprising  how  many  of 
the  clinical  signs  of  thyroid  insufficiency  are  dis- 
covered. And  it  is  equally  true  that  attempts  to 
control  these  associated  manifestations,  often  si- 
multaneously benefit  the  more  decidedly  rheumatic 
symptoms. 

Whenever  you  meet  rheumatism,  especially  the 
chronic  forms,  at  least  think  of  the  thyroid  and  its 
possible  relations  to  it. 

Epilepsy  is  one  of  the  profession's  "hardest  nuts" 
and  is  not  "easy  to  crack."  Probably  there  are  fac- 
tors involved  that  we  know  very  litle  about  as  yet, 


IN  PRACTICAL  MEDICINE  23 

such  as  the  presumed  bacillus  epilepticus,  the  ef- 
fects of  allergy  and  the  cause  and  effects  of  the  cer- 
ebral edema  which  seems  to  be  present.  Many 
clinicians  have  discovered  threads  connecting  epi- 
lepsy with  the  endocrine  glands — the  thyroid  has 
long  since  been  supposed  to  play  some  part  in  some 
cases,*  the  parathyroids  are  implicated  in  many 
other  convulsive  conditions,  perhaps  also  in  epi- 
lepsy. Just  a  few  weeks  ago  H.  A.  Knox  (4)  in  a 
paper  on  "Research  in  Epilepsy"  reports  fairly 
good  results  in  30  cases  of  epilepsy  which  were 
treated  with  desiccated  parathyroids  (2  grains 
three  times  a  day,  increasing  each  dose  by  2  grains 
each  month)  and  calcium  lactate  (1  dram  of  the 
saturated  solution  daily).  The  adrenals  are  played 
upon  so  invariably  by  the  alimentary  toxemia,  the 
most  prominent  of  all  the  findings  in  the  disease, 
and  so  progressive  a  man  as  Cotton  of  the  New 
Jersey  State  Hospital,  of  Trenton,  is  treating  scores 
of  cases  (69  were  recently  reported)  by  keeping 
this  particular  relationship  in  mind.  (5) 

Perhaps  the  gland  that  is  receiving  the  most  at- 
tention at  present  is  the  pituitary,  and  it  seems  to 
be  affected  more  than  rarely  and,  too,  pituitary 
feeding  is  reported  to  have  proved  very  useful  (6) 
and  several  personal  experiences  confirm  this.  Suf- 
fice it  to  say  that  the  glands  of  internal  secretion 


♦The  subject  of  the  relationship  of  the  thyroid  gland  to 
epilepsy  is  more  fully  discussed  in  a  recent  paper  by  the  author. 
(See  Chapter  XII.) 


24  THE  INTERNAL  SECRETIONS 

are  so  often  involved  in  epilepsy  that  they  are  our 
most  promising  field  of  present  research  in  unrav- 
eling the  mysteries  of  this  disease. 

Whenever  you  have  to  treat  epilepsy,  don't  for- 
get the  glands  of  internal  secretion.  To  do  this 
may  alter  your  treatment  in  a  most  salutary  man- 
ner. 

Neurasthenia  has  been  called  a  "cloak  with 
which  to  cover  slipshod  diagnoses" — scientifically 
speaking,  there  is  really  no  such  thing.  But  the 
patient  won't  believe  this,  for  something  is  cer- 
tainly wrong  when  they  are  supposed  to  have  "neu- 
rasthenia" and  that  "something"  is  of  a  chemical 
rather  than  a  nervous  character.  Cannon's  work 
on  the  relations  of  the  emotions  to  adrenal  activity 
is  destined  to  clear  up  many  of  our  hazy  concep- 
tions of  functional  pathology.  It  is  a  big  subject 
and  Cannon  has  written  a  whole  book  on  it;  (7) 
but  it  must  suffice  to  say  that  neurasthenia  really 
seems  to  be  nothing  more  nor  less  than  a  mani- 
festation of  functional  dysadrenia.  Permit  me  to 
read  you  two  quotations*  before  we  leave  this: 

"The  typical  neurotic  generally  has,  if  not  al- 
ways, disturbance  of  the  thyroid  gland.  The  typi- 
cal neurasthenic  probably  generally  has  disturb- 
ance of  the  suprarenal  glands  on  the  side  of  insuffi- 
ciency. The  blood  pressure  in  these  neurasthenic 
patients  is  almost  always  low  for  the  individuals, 


♦The  second  quotation  9    (from  Kinnier  Wilson's  writings) 
will  be  found  on  page  89  of  Chapter  VII. 


IN  PRACTICAL  MEDICINE  25 

and  their  circulation  is  poor.  A  vasomotor  paraly- 
sis, often  present  allows  chillings,  flushings,  cold 
or  burning  hands  and  feet,  drowsiness  when  the 
patient  is  up,  wakefulness  on  lying  down  and  hence 
insomnia.  There  may  be  more  or  less  tingling  or 
numbness  of  the  extremities."  (9) 

Whenever  you  encounter  a  neurosis,  try  to  fix 
connecting  links  between  it  and  the  endocrine 
glands;  and  you  may  succeed  more  times  than  you 
will  fail. 

Diabetes  is  an  endocrine  disease — that  is,  if  we 
believe  that  the  pancreas  has  an  internal  secretory 
function  as  the  physiologists  have  most  conclu- 
sively shown.  The  so-called  Allen  treatment  not 
merely  reduces  toxemia  (which  excites  the  ad- 
renals) but  saves  the  pancreas  (which  is  antagon- 
ized by  the  adrenals)  and  thus  "acts  both  ways." 
The  successful  treatment  of  functional  diabetes 
mellitus — not  that  form  of  the  disease  which  is  due 
to  serious  structural  change  as  in  the  diabetes  of 
youth,  cancer  of  the  pancreas,  etc. — embodies  three 
things:  (1)  relieving  the  pancreas  of  as  much  work 
as  possible,  (2)  increasing  the  pancreatic  internal 
secretion  if  this  be  feasible,  (3)  removing  toxemia 
and  modifying  the  nervous  circumstances  (stress, 
worry,  mental  fatigue),  thereby  reducing  adrenal 
excitability. 

Tuberculosis  is  never  a  local  affair;  it  can  not  be. 
Hence  the  general  reaction,  whether  toxic,  febrile, 
afebrile  or  nutritional,  or  all  of  these  combined,  also 


26  THE  INTERNAL  SECRETIONS 

affects  the  endocrine  glands  for  they  are  a  part  of 
the  body,  and,  in  fact,  they  are  the  most  sensitive 
part  of  the  body. 

It  is  strange  that  as  yet  only  a  few  men,  of  whom 
Dr.  Pottenger  here  is  probably  the  most  aggres- 
sive, are  taking  this  fact  into  consideration.  We 
have  such  a  big  fight  on  our  hands  that  all  we  can 
see  is  hygiene,  diet  and  tuberculin.  Now  all  of 
these  are  splendid,  but  why  not  seek  out  the 
changes  of  chemistry  due  to  the  effects  of  the  tu- 
berculosis on  the  endocrine  glands?  Are  there  no 
evidences  of  endocrine  involvement?  For  instance 
in  long  drawn  out  chronic  disorders  asthenia  is  uni- 
formly present,  why  not  endocrinasthenia?  This 
new  word  has  heretofore  been  called  "pluriglandu- 
lar insufficiency"  and  it  represents  an  almost  uni- 
versal concomitant  of  tuberculosis. 

We  must  not  forget  to  mention  the  frequency 
with  which  the  picture  of  dysadrenia  is  prominent 
— hyperadrenia  is  common,  with  the  circulatory 
irritability,  heart  excitement,  alimentary  spasm 
and  occasional  digestive  crises.  Later  hypodrenia 
is  invariably  present  with  asthenia  plus,  subnormal 
temperature,  low  blood  pressure  and  deficient  sym- 
pathetic tone. 

I  am  not  saying  that  the  appreciation  of  these 
endocrine  features  of  tuberculosis  is  going  "to 
revolutionize  our  conceptions  of  this  disease,"  but 
I  do  say  this: 

When  you  see  tuberculosis  remember  "endocrin- 


IN  PRACTICAL  MEDICINE  27 

asthenia"  and  if  direct  measures  are  taken  to  offset 
this  phase  of  the  symptomatology  of  tuberculosis, 
surely  no  harm  will  have  been  done. 

Syphilis — the  great  toxemia,  is  probably  re- 
sponsible for  more  organic  or  structural  diseases 
than  any  other  single  cause.  And  what  is  true 
with  bone,  nerve,  muscle  and,  in  fact,  all  tissues,  is 
equally  true  of  the  endocrine  glands.  Many  a  pitu- 
itary tumor  or  brain  condition  influencing  this 
gland  is  of  luetic  origin.  Many  a  "hidden  syphilis" 
is  insidiously  affecting  function  and  this  does  not 
miss  the  endocrine  glands  even  if  it  may  not  be 
causing  actual  structural  change  in  them. 

I  am  convinced  that  at  least  a  part  of  the  consti- 
tutional manifestations  of  syphilis,  and  especially 
those  which  may  be  connected  with  the  sympa- 
thetic nervous  system,  are  directly  the  result  of 
endocrine  changes  resulting  from  the  toxic  effects 
of  this  infection. 

We  know  that  syphilis  has  the  peculiar  capacity 
of  wreaking  its  vengeance  on  the  innocent;  and 
fully  one  half — I  am  speaking  offhand — of  inher- 
ited endocrine  defects,  functional  or  organic,  are 
traceable  to  syphilis.*  The  feeble  minded,  the  de- 
fectives, the  incompetents  and  many  who  may  not 
be  so  decidedly  marked,  but  none  the  less  have  a 
facility  for  functional  derangements — whose  con- 


*This  is  probably  an  overstatement,  though  lues  is  certainly 
a  universal  scourge;  and  is  often  a  factor  in  ductless  glandular 
troubles. 


28  THE  INTERNAL  SECRETIONS 

stitutions  are  "not  right" — in  reality  may  be  suffer- 
ing from  the  inherited  defects  caused  by  syphilis.* 

Whenever  you  discover  syphilis,  look  for  its 
chemical  effects — the  functional  pathology  that  it 
so  often  causes  and,  too,  whenever  you  find  well- 
defined  organic  endocrine  disease  think  at  once  of 
syphilis  and  keep  on  thinking  of  it  until  it  is  ruled 
out,  or  no  longer  a  question. 

In  closing  I  will  take  this  excellent  opportunity 
to  offset  a  tendency  to  discount  statements  which 
seem  to  indicate  that  I  "see  ductless  glands  in 
every  case,"  as  one  man  put  it  the  other  day,  by 
reminding  you  that  there  are  ductless  glands  in 
every  case!  I  will  supplement  this  by  adding  that 
they  are  very  important  and  responsible  little  or- 
gans, for  not  only  do  they  serve  the  body  and  suffer 
with  the  body;  but  when  their  first  pathology  is 
discovered  and  suitably  treated,  a  new  aspect  many 
times  is  put  upon  a  case. 

REFERENCES 

1.  Editorial,  "Functional  Medicine,"  New  York  Medi- 
cal Journal,  1916,  civ,  1155. 

2.  Editorial  Note,  "A  Therapeutist's  View  on  Cancer." 
Am.  Jour.  Clin.  Med.,  1917,  xxiv,  181. 

3.  Harrower,  Henry  R.,  "The  Relation  of  the  Internal 
Secretions  to  Rheumatism,"  etc.  Amer.  Med.,  1915,  xxl,  363. 
(This  is  Chapter  XI  of  this  book.) 

4.  Knox,  H.  A.,  "Research  in  Epilepsy."  New  York 
Med.  Jour,  1917,  cv,  406. 


♦This  does  not  necessarily  mean  that  the  unfortunate  actu- 
ally has  inherited  syphilis,  although  it  is  too  often  discoverable 
by  our  present  methods  of  clinical  research. 


IN  PRACTICAL  MEDICINE  29 

5.  Cotton,  H.  A.,  et  al.,  "The  Pathogenesis  and  Treat- 
ment of  Epilepsy."    New  York  Med.  Jour.,  1916,  civ,  532. 

6.  Editorial,  "The  Prospects  of  Anterior  Pituitary 
Therapy."  Endocrinology,  1917,  i,  13.  See  also  Joughin, 
J.  L.,  "Glandular  Therapy  and  the  Epileptic  Syndrome," 
New  York  Med.  Jour.,  1916,  ciii,  693;  and  Tucker,  B.  R., 
"The  Relation  of  Hypopituitarism  and  Epilepsy."  Va.  Med. 
Semi-Monthly,  1916,  xxi,  1. 

7.  Cannon,  W.  B.,  "Bodily  Changes  in  Pain,  Hunger, 
Fear  and  Rage."    New  York,  1915,  Appletons. 

8.  Editorial,  "Neurasthenia — Suprarenal  Insufficiency," 
Jour.  A.  M.  A.,  1915,  lxv,  2166. 

9.  Kinnier-Wilson,  S.  A.,  The  Clinical  Importance  of 
the  Sympathetic  Nervous  System,"  London,  1913.  See  also 
Harrower,  Henry  R.,  "The  Adrenal  Glands  and  their  Sig- 
nificance in  General  Practice."  Med.  Rev.  of  Reviews,  1917, 
xxxii,  335.     (This  is  Chapter  VII  of  this  book.) 


IV 

THE  INCONSPICUOUS,  EVERY-DAY 
FORMS  OF  THYROID  INSUFFICIENCY 

THE  so-called  "minor  thyroid  insufficiency"  oc- 
curs in  the  routine  work  of  every  physician,  every 
day.  Very  often  it  is  entirely  overlooked.  It  is  the 
principal  cause  of  quite  a  number  of  widely  varying 
conditions  and  a  factor  of  importance  in  many 
others.  The  thyroid  gland  has  been  aptly  called 
"the  keystone  of  the  endocrine  arch";  and  we  are 
beginning  to  realize  that  the  glands  of  internal  se- 
cretion play  a  much  more  important  role  than 
many  of  us  had  hitherto  imagined.  In  fact,  they 
are  the  prime  factors  in  the  regulation  of  metabo- 
lism; dominate  the  nervous  system,  more  especially 
the  sympathetic;  and  are  altogether  indispensable 
to  the  maintenance  of  the  physiologic  harmony  of 
the  body. 

Our  interest  in  these  glands,  then,  by  no  means 
should  be  limited  to  the  mere  consideration  of  defi- 
nite disease  in  one  or  more  of  them.  We  should 
seek  rather  to  appreciate  the  insidious  and  insig- 
nificant minor  aberrations  from  the  normal,  and  in 
so  doing  in  many  cases  we  will  be  able  to  forestall 
the  more  serious  organic  manifestations  which 
later  assert  themselves.  (My  use  of  the  word  "in- 
Read  before  the  Riverside  County  Medical  Society,  De- 
cember 13,  1915,  and  reprinted  from  the  California  State  Jour- 
nal of  Medicine  (San  Francisco),  May,  1916. 

(30) 


IN  PRACTICAL  MEDICINE  31 

significant"  refers  rather  to  the  ease  with  which 
these  conditions  are  appreciated,  than  to  their  com- 
parative importance,  for  these  aberrations  are  cer- 
tainly much  more  important  than  yet  appears  to 
many  physicians.) 

As  we  occupy  ourselves  in  searching  for  the 
early,  minor  manifestations  of  internal  secretory 
disturbance,  we  will  be  able  not  merely  to  forestall 
the  more  serious  organic  diseases,  but  will  discover 
that  unsuspected  associated  symptoms,  from  chil- 
blains to  nocturnal  enuresis,  or  rheumatism  to  mel- 
ancholia, will  be  modified  by  organotherapeutic 
measures  which  may  have  been  directed  at  some 
entirely  different  condition. 

Most  of  our  practical  information  on  this  sub- 
ject has  been  acquired  accidentally.  A  physician  is 
investigating  a  certain  train  of  symptoms  and  he 
casually  glimpses  something  he  had  not  been  look- 
ing for;  or  some  concomitant  condition  at  which  he 
had  not  been  especially  directing  his  efforts,  is 
cleared  up  and  a  new  therapeutic  procedure  is  born. 
Such  experiences  have  laid  the  foundation  for  prac- 
tical organotherapy,  and  while  this  form  of  thera- 
peutics is  often  altogether  empirical,  we  are  or 
should  be  thankful  that  we  can  bring  about  results 
that  are  nothing  short  of  marvelous,  even  though 
we  cannot  quite  explain  the  "how"  or  the  "why." 

When  the  functions  of  the  thyroid  gland  were 
just -beginning  to  be  appreciated  some  25  years  ago, 
most  of  those  who  studied  the  matter  did  so  from 


32  THE  INTERNAL  SECRETIONS 

the  standpoint  of  the  influence  upon  the  organism 
of  the  absence,  either  congenital  or  experimental, 
of  this  gland.  A  year  or  two  later,  when  Murray, 
then  of  Newcastle,  first  administered  a  preparation 
of  animal  thyroids,  he  gave  it  to  a  woman  suffering 
from  myxedema,  and  for  a  long  time  thyroid  ther- 
apy was  confined  to  the  serious  major  thyroid  syn- 
dromes. Both  these  circumstances  have  tended 
to  obscure  the  question  of  the  less  obvious  thyroid 
disorders,  and  for  a  long  time  the  use  of  this  new 
remedy  was  limited  to  the  treatment  of  those  cases 
in  which  there  was  a  marked  affection  or  entire  ab- 
sence of  the  organ. 

An  important  result  of  this  still  persists.  Until 
quite  recently  the  generally  recommended  dose  of 
thyroid  was  altogether  too  large,  at  least,  in  the 
majority  of  the  cases  in  which  it  is  to  be  given. 
This  was  doubtless  due  to  the  fact  that  the  original 
dosage  as  indicated  in  the  various  pharmacopeias 
was  based  upon  experiences  in  the  treatment  of 
athyroidic  individuals.  It  is  true  that  a  commonly 
suggested  dose — five  grains  three  times  a  day — 
may  be  none  too  much  for  myxedema  or  cretinism. 
Occasionally  it  may  be  increased  advantageously 
above  this  figure,  for  in  organotherapy  "there  is  no 
dose  save  dose  enough" — the  only  difficulty  being 
how  to  determine  when  "enough"  is  given;  but 
since  we  are  now  using  thyroid  in  a  host  of  other 
disorders  related  to  functional  minor  hypothyroid- 
ism we  must  begin  with  much  smaller  doses,  say 


IN  PRACTICAL  MEDICINE  33 

an  average  of  one-quarter  or  one-half  a  grain  three 
times  a  day. 

This  has  had  an  unfortunate  influence  upon  the 
practical  consideration  of  this  subject.  Our  atten- 
tion having  been  directed  to  an  important  series  of 
facts,  we  have  overlooked  much  else  that  is  of 
greater  importance  in  every-day  medicine.  After 
all,  the  major  thyroid  insufficiencies  are  not  so  very 
common.  We  see  them  occasionally  and  usually 
they  interest  us  only  moderately,  for  the  treatment 
is  now  fairly  well  understood  and  there  is  little  to 
do  save  to  follow  the  well-established  procedures 
and  supply  the  lack  that  nature  or  the  surgeon  ac- 
cidentally has  brought  about.  On  the  other  hand 
the  minor  cases  of  hypothyroidism  complicate  the 
work  of  the  general  practitioner  in  such  disorders 
as  nocturnal  enuresis,  headache,  cold  feet  and 
hands  or  chilblains.  The  dermatologist  is  con- 
cerned because  of  the  connection  of  hypothyroid- 
ism with  many  dermatoses,  such  as  psoriasis,  pru- 
rigo, eczema  or  herpes.  The  internist  finds  a  rela- 
tion between  this  condition  and  certain  forms  of 
rheumatism  and  cardiac  disorders.  The  neurolo- 
gist knows  that  neurasthenia,  melancholia,  many 
forms  of  insanity  and  some  of  the  psychoses  may 
be  purely  thyroid  in  origin  and  as  one  prominent 
alienist  once  put  it,  "the  most  important  single 
remedy  in  the  asylum  is  probably  thyroid  extract." 
The  gynecologist  finds  the  thyroid  a  direct  cause  of 
many  functional  genital  conditions  and  has  learned 


34  THE  INTERNAL  SECRETIONS 

that  it  is  so  intimate  with  the  ovaries  that  disorders 
of  them  cannot  occur  without  some  reflex  influence 
upon  thyroid  activity,  he  also  has  found  in  thyroid 
extract  a  most  useful  means  of  treating  many 
forms  of  female  disease,  especially  amenorrhea  and 
dysmenorrhea  of  certain  forms.  The  surgeon  finds 
the  thyroid  more  of  an  unmitigated  nuisance  than 
a  help,  although  a  connection  between  thyroid  ac- 
tivity and  bone  growth  is  reported  and  the  con- 
trol by  this  gland  of  development  makes  it  of  im- 
portance in  the  consideration  of  a  number  of  de- 
formities and  dystrophies.  Last,  but  not  least,  in 
pediatric  practice  thyroid  therapy,  and  of  course 
the  physiologic  influence  of  this  gland,  is  all  im- 
portant; and  thyroid  extract  is  one  of  the  most 
commonly  used  organotherapeutic  remedies  in  the 
treatment  of  many  infantile  disorders.  We  have 
already  mentioned  its  possible  utility  in  nocturnal 
enuresis;  and  in  many  nutritional  disturbances, 
most  of  which  are  of  endocrine  origin,  the  thyroid 
is  the  most  commonly  disordered  gland.  In  fact, 
one  can  hardly  find  a  nutritional  dyscrasia  in  chil- 
dren without  very  quickly  tracing  a  part  of  its 
origin,  at  least,  to  the  thyroid  gland.  Such  mani- 
festations as  mental  dullness,  enlarged  tonsils  or 
adenoids,  nasal  or  bronchial  catarrh,  dry,  rough 
skin  with  coarse  hair,  as  well  as  defective  speech 
and  occasionally  soft  bones,  are  all  indications  of  a 
possibly  deficient  thyroid  activity.  The  metabolic 
changes  in  rickets  and  marasmus  are  undoubtedly 


IN  PRACTICAL  MEDICINE    .  35 

partially  due  to  disturbances  in  what  Gauthier  calls 
"the  thyroid  apparatus,"  i.  e.,  the  thyroid,  thymus 
and  parathyroids;  and  it  seems  quite  certain  that 
the  idea  that  this  disease  was  due  solely  to  faulty 
feeding  or  to  the  impossibility  of  breast  feeding, 
must  now  be  relegated  to  the  background  and  the 
thyroid  and  associated  glands  be  given  first  con- 
sideration. It  is  quite  remarkable  how  very  small 
doses  of  thyroid — one-twentieth  to  one-quarter 
grain  three  or  four  times  a  day  for  some  weeks — 
will  modify  many  of  the  manifestations  just  men- 
tioned— in  adults  as  well  as  children.  It  is  quite 
safe  to  say  that  the  physician  who  remembers  the 
extreme  intimacy  of  the  thyroid  gland  with  dis- 
turbances of  nutrition  will  be  much  more  successful 
in  their  treatment. 

Apropos  of  this,  an  interesting  statement  by  Isa- 
belle  Thompson  Smart  of  New  York  (Med.  Rev.  of 
Revs.,  1915,  p.  269)  is  worth  quoting:  "The  subtle 
influence  (of  thyroid)  upon  the  hormone  balance 
regulates  in  a  mysterious  way  the  whole  of  the  in- 
ternal secretory  activities.  We  cannot  always  ex- 
plain why  thyroid  extract  is  such  a  remarkable 
remedy,  but  we  are  satisfied  to  know  the  extraordi- 
nary results  that  frequently  follow  its  use  where 
there  is  a  metabolic  disturbance  of  obscure  origin 
and  in  which  there  are  none  of  the  indications  of 
cretinism.  An  unscientific  but  very  satisfactory 
means  of  treating  this  large  class  of  cases  is  to  give 
thyroid  extract,  as  one  physician  says,  'like  a  hit 


36  THE  INTERNAL  SECRETIONS 

in  the  dark/  and  while  misses  are  not  uncommon, 
the  physician  who  does  this  will  be  surprised  at 
their  comparative  infrequency." 

When  we  recall  the  fact  that  the  glands  of  in- 
ternal secretion  are  inextricably  related  to  one  an 
other  and  also  that  one  cannot  harm  one  without 
disturbing  the  harmonious  interrelation  of  the 
others,  the  importance  of  this  subject  begins  to 
grow  upon  us.  Every-day  circumstances  such  as 
the  emotions,  toxemia  of  alimentary  and  other 
origin,  disease  of  all  kinds,  genital  derangement  of 
ever  so  slight  a  degree,  especially  in  the  female, 
and  even  the  weather,  may  stimulate  or  depress, 
as  the  case  may  be,  one  or  more  of  these  hormone- 
producing  organs  with  results  which  vary  very  de- 
cidedly in  their  clinical  manifestations  and  seri- 
ousness. 

I  cannot  refrain  from  making  the  briefest  ref- 
erence to  a  condition  which  has  been  aptly  termed 
"the  jerry-built  constitution/'  The  name  is  almost 
self-explanatory.  By  far  the  most  important  factor 
in  such  individuals  is  a  thyroid  instability.  These 
individuals  "catch  everything,"  they  are  in  a  state 
of  low  metabolic  activity,  their  urinary  solids  are 
low  and  the  acidity  is  high.  They  are  toxic.  Neuras- 
thenia is  common  in  such  cases.  They  are  none  too 
bright  in  their  studies  or  their  business.  They  are 
the  skim-milk  of  humanity,  and  how  much  of  it 
there  seems  to  be.  Study  the  internal  secretory 
capacity  of  such  individuals;  enhance  the  action  of 


IN  PRACTICAL  MEDICINE  37 

the  thyroid,  at  the  same  time  neutralizing  the  ten- 
dency toward  acidemia  and  clean  out  the  bowels, 
and  there  will  be  a  metamorphosis  that  is  some- 
times astonishing.  Right  here  I  want  to  say  that 
the  treatment  mentioned  exclusive  of  organother- 
apy is  by  no  means  so  efficient  and  I  have  come  to 
the  conclusion  that  the  hormones  really  do  the 
work  and  the  re-establishment  of  a  normal  alkalin- 
ity of  the  blood  and  the  removal  of  as  many  of  the 
toxic  products  as  possible  merely  puts  Nature  in 
a  position  to  respond  to  the  stimuli  to  which  she 
is  accustomed  and  the  lack  of  which  is  such  a  po- 
tent factor  in  the  etiology  of  many  of  the  cases 
mentioned.  The  detoxicating  procedures  are  nega- 
tive treatment,  if  I  may  so  term  it ;  while  the  organ- 
otherapy is  positive  treatment.  The  former  is  good, 
for  it  gives  Nature  a  chance;  but  both  are  better, 
because  the  hormones  thus  administered  give  Na- 
ture a  boost. 

You  realize,  of  course,  that  we  cannot  begin  to 
consider  the  whole  gamut  of  minor  thyroid  dis- 
orders to-night.  Their  ramifications  extend  into 
every  phase  of  medicine.  Leopold  Levi  and  Baron 
Henri  de  Rothschild,  of  Paris,  have  written  two 
fairly  large  books  on  this  single  subject;  and  in 
their  most  recent  publication  the  relation  of  the 
thyroid  to  each  of  the  important  disorders,  acute 
and  chronic,  is  thoroughly  discussed.  Many  dis- 
orders which  we  have  mentioned  incidentallv  are 
given  the  prominence  of  a  chapter  to  themselves. 


38  THE  INTERNAL  SECRETIONS 

But  before  closing  I  would  like  to  lend  a  little  more 
emphasis  to  some  points  regarding  diagnosis,  as 
well  as  to  the  administration  and  dosage  of  thyroid 
extract. 

The  diagnosis  of  minor  hypothyroidism  is  com- 
paratively simple.  Most  often,  I  must  admit,  it 
is  presumed  to  be  present  and  "diagnosed"  by  the 
therapeutic  test.  Several  of  the  commonest  symp- 
toms have  already  been  mentioned  and  for  conveni- 
ence it  may  be  well  to  quote  from  a  recent  mono- 
graph by  Lewellys  F.  Barker,  of  Baltimore,  entitled 
"Some  of  the  Commoner  Types  of  Diseases  of  the 
Endocrine  Glands": 

In  examining  children  for  minor  hypothyroid- 
ism, three  principal  points  should  be  kept  in  mind: 
(1)  retarded  growth;  (2)  habitual  constipation, 
and  (3)  dullness  in  the  schoolroom.  In  adults  the 
most  important  symptoms  are  (1)  endogenous 
obesity;  (2)  persistent  constipation;  (3)  a  dry. 
harsh  skin;  (4)  subjective  feelings  of  cold,  and  (5) 
recurring  drowsiness  in  the  daytime.  Barker  ad- 
vises the  therapeutic  test  in  all  cases  where  there 
is  any  doubt  of  the  presence  of  a  condition  of  this 
nature;  in  other  words,  this  eminent  internist  sug- 
gests recourse  to  empiricism,  and  he  undoubtedly 
is  right. 

Some  other  symptoms  which  have  directed  at- 
tention to  a  thyroid  insufficiency  which  had  been 
entirely  overlooked,  may  be  mentioned.  They  are, 
however,  not  infallible  signs:    Cracked  and  brittle 


IN  PRACTICAL  MEDICINE  39 

finger  nails;  loss  of  the  outer  third  of  the  eye- 
brows; twitching  or  blinking  of  the  eyelids;  fleet- 
ing and  indefinite  joint  pains;  low  total  solids  in 
the  urine;  sensitiveness  to  cold  and  especially  the 
need  for  an  unduly  large  quantity  of  bedclothes; 
snoring  (without  other  good  reasons  therefor) ;  re- 
duced resistance  to  infections,  especially  of  the 
skin,  as  acne,  etc.  To  these  must  be  added  the 
well-known  symptoms  of  major  hypothyroidism, 
though,  of  course,  in  the  "minor"  cases  they  are  not 
so  well  marked. 

Thyroid  extract  is  a  most  useful  remedy  and  like 
most  drugs  of  its  importance  is  worthy  of  much 
more  study  and  far  greater  clinical  application. 
Small  dosage  is  always  the  rule.  A  quarter  of  a 
grain  is  my  usual  initial  dose.  It  may  be  repeated 
from  two  to  six  times  a  day.  Rarely  is  it  necessary 
to  give  more  than  three  grains  a  day  in  divided 
dosage.  Occasionally  one  meets  a  patient  who 
needs  thyroid  but  cannot  tolerate  it;  in  such  cases 
it  is  well  to  try  giving  the  whole  day's  dose,  not 
more  than  one-half  grain  at  first,  increasing  later 
to  one  and  one-half  or  two  grains,  at  bedtime.  This 
obviates  some  of  the  inconveniences  with  the  heart 
and  respiration.  In  this  class  of  cases  Heinrich 
Stern,  of  New  York,  gives  sodium  cacodylate  in 
small  doses  with  the  thyroid.  He  finds  that  this 
mitigates  the  inconveniences  of  an  idiosyncrasy  to 
this  remedy. 

Thyroid  must  be  given  for  some  time  to  be  most 


40  THE  INTERNAL  SECRETIONS 

effective.  The  French  method  appeals  to  me  most. 
They  give,  say,  one  centigram  (one  and  one-half 
grains)  of  thyroid  per  day,  divided  into  three  or 
more  doses,  and  continue  thus  for  one  week.  The 
drug  is  then  omitted  for  a  week  or  even  longer, 
and  then  begun  again  for  another  period  of  a  week, 
using  the  same  or  a  slightly  larger  dose,  then  omit- 
ting it  for  another  week  or  more,  and  so  on.  Occa- 
sionally individuals  supersensitive  to  thyroid  medi- 
cation may  establish  a  tolerance  to  a  given  dose, 
and  after  reducing  the  amount  and  starting  again, 
it  may  be  found  that  they  are  able  to  take  very 
much  larger  doses  with  none  of  the  previous  symp- 
toms of  intolerance. 

In  many  cases  where  thyroid  is  indicated,  espe- 
cially in  obese  women  who  are  taking  thyroid  to 
facilitate  reduction,  pluriglandular  therapy  may  be 
helpful.  Corpus  luteum  given  with  the  thyroid  is 
sometimes  of  much  assistance,  especially  in  neuras- 
thenic women  and  those  at  or  near  the  menopause. 
In  asthenic  cases  with  a  considerable  degree  of 
muscular  weakness  and  constipation  pituitary  is 
given  in  conjunction  with  thyroid  with  good  re- 
sults. 

Pituitary  (whole  gland)  is  often  given  advan- 
tageously with  thyroid  in  children  who  have  hypo- 
thyroidism. This  is  especially  so  in  cases  with  mal- 
development  and  dullness.  The  dose  may  consist 
of  one-quarter  to  one-half  grain  with  half  as  much 
thyroid  three  or  four  times  a  day.    The  amount  of 


IN  PRACTICAL  MEDICINE  41 

pituitary  may  be  increased  more  frequently  than 
the  thyroid,  giving  finally,  say,  two  and  one-half 
or  more  grains  of  pituitary  and  one-half  grain  of 
thyroid  at  a  dose. 

An  important  point  regarding  the  dosage  of  thy- 
roid in  children  is  the  fact  that  the  amount  given 
is  not  regulated  by  the  body  weight  or  age  of  the 
child.  Dosage  depends  solely  upon  individual  sus- 
ceptibility. The  only  way  to  establish  a  suitable 
dose  for  a  given  case  is  to  start  with  a  small  dose, 
say,  one-tenth  or  even  one-twentieth  of  a  grain  at 
the  usual  intervals,  giving  increased  doses  very 
carefully  until  evidences  of  intolerance  are  noted. 
Then  stop  the  medication  for  a  period  and  recom- 
mence again  with  the  previous  dose  or  slightly  less. 

An  important  point  to  which  I  have  never  seen 
attention  drawn  concerns  the  label-dosage  of  sev- 
eral thyroid  preparations  on  the  market.  Prepara- 
tions of  this  character  are  usually  given  in  tablet 
form,  as  it  is  most  convenient  and  quite  satisfac- 
tory. Manufacturers  indicate  the  contents  of  their 
tablets  in  three  ways  on  the  labels:  (1)  5-grain 
tablets;  (2)  5-grain  tablets,  each  tablet  represent- 
ing 3  grains  of  desiccated  thyroid  substance,  and 
(3)  tablets  representing  5  grains  of  fresh  thyroid 
glands.  These  figures  are  mentioned  merely  for 
convenience,  since  5-grain  tablets  of  thyroid  are 
not  used  so  much  these  days.  It  will  be  clear  that 
(1)  does  not  contain  5  grains  of  the  active  remedy 
of  thyroid  with  no  excipient  to  bind  it  or  to  facili- 


42  THE  INTERNAL  SECRETIONS 

tate  its  rapid  disintegration.  I  much  prefer  the 
second  way  of  expression,  the  size  of  the  tablet  is 
merely  for  manufacturing  convenience  and  the 
amount  of  active  constituent  is  definitely  stated. 
Regarding  (3)  I  cannot  understand  why  a  firm 
should  insist  on  denoting  the  amount  of  fresh  sub- 
stance, rather  than  the  standard  (U.  S.  P.,  in  this 
particular  instance)  preparation  of  dried  gland. 
This  may  be  the  cause  of  trouble.  For  instance:  A 
physician  is  giving  a  Parke,  Davis  &  Co.  tablet,  5 
grains  at  a  (hypothetical)  dose.  For  some  reason 
or  another  the  treatment  is  continued  with  a  Bur- 
roughs, Wellcome  &  Co.  tabloid,  but  it  is  not  no- 
ticed that  "Tabloid  Thyroid  Gland  Gr.  5"  repre- 
sents fresh  substance,  or  only  one-fifth  as  much  of 
the  dried  gland  as  had  been  previously  given!  To 
reverse  this  experience  would  be  much  worse,  for 
then  a  change  of  brand  would  entail  a  sudden  mul- 
tiplication of  the  desired  dose  by  five!  Parenthet- 
ically it  may  be  remarked  that  this  last-mentioned 
firm  puts  a  "Tabloid  Thyroid  Gland  Gr.  1-10/' 
which  contains  only  one-fiftieth  of  a  grain  of  the 
dried  gland. 

There  is  a  good  deal  more,  but  it  will  have  to 
be  left  for  another  time.  Suffice  it  to  say  that  minor 
thyroid  insufficiencies  are  as  common  in  the  aver- 
age run  of  patients  as  orange  trees  are  here,  only 
they  are  not  always  so  obvious. 

Let  us  cultivate  our  sense  of  discernment  so  that 
cases  of  this  kind  will  not  slip  by  unnoticed  again. 


V 

PLURIGLANDULAR  INSUFFICIENCY:    ITS 
INCIDENCE  AND  TREATMENT 

PLURIGLANDULAR  insufficiency,  or  hypo- 
endocrinism,  is  a  comparatively  recent  term,  rarely 
found  in  the  medical  literature  published  seven  or 
more  years  ago.  To  appreciate  the  full  import  of 
the  subject  which  has  been  allotted  to  me,  it  is  nec- 
essary, first,  to  realize  the  fact  that  the  endocrine 
system  is  a  very  essential  part  of  the  organism, 
since  by  its  various  internal  secretions  practically 
the  whole  of  the  workings  of  the  body  are  regu- 
lated and  correlated.  It  might  be  compared  to  the 
magneto  of  the  automobile  or,  perhaps,  to  the  ex- 
change of  a  telephone  system. 

In  his  comment  in  the  New  York  Medical  Jour- 
nal (1)  on  the  advanced  position  taken  by  a  Com- 
mittee appointed  by  the  Congresso  della  Societa 
Medica  Italiana  in  1912,  the  editor  says:  "One  can- 
not but  be  impressed  by  the  vast  field  which  the 
ductless  glands  have  steadily  invaded,  in  keeping 
with  the  conclusions  announced  nearly  ten  years 
ago,  in  this  country,  that  these  organs  were  second 
to  none  in  the  body  in  their  bearing  upon  physiol- 
ogy, pathology,  and  clinical  medicine. "  The  Com- 
mittee representing  these  Italian  investigators  in 
their  official  report  to  the  Congress   (2)  asserted 


Prepared  for  a  "Special  Internal  Secretions  Number"  of  "The 
Practitioner"    (London),  published  January,  1915. 

(43) 


44  THE  INTERNAL  SECRETIONS 

that:  'The  internal  secretions  manifest  an  influ- 
ence upon  the  anomalies  of  growth,  morphology, 
and  organic  metabolism;  on  nutrition  and  inherent 
excitability  of  the  nervous  system;  on  resistance  to 
infections  and  intoxications,  as  well  as  a  prepon- 
derating role  in  the  causation  of  dyscrasias  and 
morbid  temperaments."  They  also  conclude  that 
the  equilibrium  of  the  nervous  system,  the  sympa- 
thetic in  particular,  may  be  regarded  as  maintained 
by  the  internal  secretions  and  that  in  nervous  dis- 
eases per  se  they  act  probably  as  indirect  or  predis- 
posing factors. 

The  active  principles  of  these  internal  secretions 
are  now  generally  called  hormones,  and  we  are  be- 
ginning to  realize  that  they  are  a  factor  of  extreme 
importance  in  the  regulation  of  metabolism.  In  the 
body  every  motive  force  is  balanced  by  a  retarding 
force  and  this  nice  balance  is  essential  to  health; 
hence  if  one  or  another  of  these  factors  gain  the 
ascendency,  or  is  diminished  in  activity,  disorgan- 
ization must  naturally  result  and  the  extent  of  this 
disorganization  can  hardly  be  confined  to  the  single 
area  in  which  it  is  initiated. 

The  intimate  relations  of  the  secretions  of  the 
various  endocrine  organs  predicate  pluriglandular 
disturbance  as  the  result  of  an  initial  monoglandu- 
lar  disorder,  thus  explaining  the  dictum  of  Bayard 
Holmes  (3) :  "During  the  past  year  much  evidence 
has  accumulated  to  show  that  diseases  of  the  duct- 
less glands  are  usually  plural  rather  than  isolated 


IN  PRACTICAL  MEDICINE  45 

and  single.  Pluriglandular  disease  is  the  rule  rather 
than  the  exception." 

This  position  is  substantiated  by  Mullaly  (4), 
who  states  that  from  a  study  of  the  autopsy  records 
at  the  Royal  Victoria  Hospital,  Montreal,  "In  the 
infrequent  autopsies  in  cases  of  ductless  gland  dis- 
orders pathological  changes  were  observed  in  more 
than  one  of  the  ductless  glands." 

Functional  disorders  of  many  varieties  may  be 
either  directly  due  to,  or  intimately  associated  with, 
changes  in  the  various  hormone  stimuli  which  are 
so  essential  to  the  maintenance  of  the  chemical  bal- 
ance upon  which  the  intricacies  of  metabolism  de- 
pend. Many  of  these  disorders  are  already  included 
in  our  present-day  classification  of  disease  and  are 
considered  among  the  ''disorders  of  the  internal  se- 
cretory glands";  in  most  of  these  cases,  however, 
the  disturbance  is  prominent  in  one  of  the  glands, 
and  among  these  we  recall  thyroid  insufficiency, 
the  major  form  or  myxedema  and  the  minor  form, 
sometimes  known  as  Hertoghe's  syndrome  (myxe- 
deme  fruste),  adrenal  insufficiency  or  Addison's 
disease,  Langerhansian  insufficiency  or  pancreatic 
diabetes,  parathyroid  insufficiency  or  tetany,  and 
numerous  other  disorders  of  function  resulting: 
from  disturbance  in  the  internal  secretory  activi- 
ties of  the  gonads,  hypophysis,  epiphysis,  etc. 

Harry  Campbell,  in  his  masterly  study  of  the  role 
of  the  blood  plasma  (5)  rightly  intimates  that  the 
blood  plasma  carries  a  host  of  varying  chemical 


46  THE  INTERNAL  SECRETIONS 

messengers  or  hormones  whose  balance  is  essential 
to  the  proper  regulation  of  the  numerous  bodily- 
functions.  This  explains  why  the  normal  content 
of  the  chromaffin  principle  does  not  exert  the  same 
action  as  when  a  dose  of  adrenalin  is  administered 
— in  the  normal  amounts  in  which  it  is  found  in 
the  blood  it  is  balanced  by  the  Langerhansian  prin- 
ciple. 

Campbell  considers  that  cell  activity  is  properly 
divided  into  the  egoistic  and  the  altruistic  cell  func- 
tions. The  former  consists  in  the  maintenance  of 
individual  cell  activity,  while  the  latter  concerns 
the  supply  to  the  organism  as  a  whole  of  certain 
services,  probably  brought  about  by  the  hormones, 
such  as  are  exemplified  in  the  numerous  functional 
relationships  between  organs.  This  so-called  "al- 
truistic" function  is  of  extreme  importance,  for  the 
cell  itself  may  seem  to  all  intents  and  purposes 
quite  healthy  and  yet  still  gravely  fail  in  its  altru- 
istic functioning — a  failure  which,  small  though  it 
be,  may  suffice  to  disorganize  the  delicate  hormonic 
balance.  A  consideration  of  these  complex  inter- 
relations* will  establish  the  extreme  importance  of 
the  hormone  equilibrium,  and,  of  course,  its  disturb- 
ances. 

There  are  two  forms  of  endocrine  disorder — or- 
ganic and  functional.  The  former,  fortunately  rare, 


*For  a  fuller  discussion  of  this  question,  see  Chapter  III, 
"The  Hormone  Balance,"  in  Practical  Hormone  Therapy  (Bail- 
liere),  by  the  writer  of  this  article. 


IN  PRACTICAL  MEDICINE  47 

is  usually  diagnosed  only  when  the  changes  are 
permanent;  it  is,  therefore,  very  difficult  to  treat 
satisfactorily.  The  latter,  on  the  other  hand,  is 
extremely  common,  it  is  frequently  overlooked, 
and,  when  its  presence  is  appreciated  and  put  under 
treatment,  it  responds  in  an  encouraging  way. 
Hence  the  principal  effort  of  the  writer  will  be  to 
emphasize  the  frequency  and  importance  of  func- 
tional insufficiencies  of  the  endocrine  organs,  rather 
than  the  definite  organic  diseases  of  these  glands. 
One  can,  however,  advantageously  refer,  in  pass- 
ing, to  several  important  papers  and  case  reports 
which  outline  the  pathology  of  those  serious  or- 
ganic conditions  which  combine  to  form  the  "plu- 
riglandular syndrome." 

One  of  the  most  pronounced  cases  of  organic 
pluriglandular  disease  was  recently  reported  by 
Maase,  (6)  the  essential  facts  being  briefly  recapit- 
ulated here:  The  patient  was  a  Russian  girl  aged 
24,  with  an  epileptic  and  diabetic  ancestry.  Normal 
in  every  way  till  18,  she  then  developed  ophthalmo- 
plegia. At  20  she  developed  a  myxedematous  state 
attended  by  suppression  of  the  menses.  Glycosuria 
was  found  and  a  positive  Wassermann  reaction; 
later  a  spinal  curvature  was  discovered.  There  was 
a  shrinkage  in  the  body  measurements  represented 
by  various  deformities.  The  bone  condition  some- 
what resembled  osteomalacia.  Death  occurred  un- 
expectedly from  erysipelas.  At  the  autopsy  the 
hypophysis,  normal  in  size,  was  adherent    to    the 


48  THE  INTERNAL  SECRETIONS 

bone  and  of  firm  consistence.  Thymus  remains 
were  quite  abundant,  while  the  thyroid  was  abnor- 
mally small  in  both  lobes.  The  pancreas  was  small, 
consisting  largely  of  fat  and  connective  tissue.  The 
ovaries  were  abnormally  small  and  showed  no 
Graafian  follicles.  The  bones  were  much  thinned 
and  brittle,  the  liver  was  fatty.  The  adrenals  alone 
of  all  the  endocrine  glands  seemed  to  be  normal, 
so  that  the  case  may  be  termed  subtotal  or  hypo- 
endocrinism.  The  other  organs  were  normal,  save 
that  the  heart  exhibited  the  changes  to  be  expected 
after  death  from  erysipelas. 

In  the  Italian  medical  literature  of  the  past  year 
Consolazio,  (7)  Bianchi,  (8)  and  Zilocchi  (9)  have 
contributed  interesting  monographs  on  this  sub- 
ject. In  France,  Costa  (10)  and  Rebattu  (11)  have 
discussed  this  subject,  and  Parhon  and  his  associ- 
ates (12)  have  experimentally  produced  conditions 
in  animals  allied  to  the  pluriglandular  syndrome. 
All  of  these  communications  consider  the  serious 
organic  conditions,  and  while  there  is  undoubted 
advantage  in  studying  this  phase  of  the  subject,  it 
is  of  far  less  immediate  practical  value  than  the 
consideration  of  the  much  more  frequent  functional 
disturbances  which,  because  of  their  insidious  on- 
set, frequently  are  entirely  overlooked. 

Costa  (10)  states  that  nice  distinctions  between 
conditions  due  to  the  various  ductless  gland  dis- 
orders are  very  difficult  to  make,  since  the  internal 
secretory  glands  all  have  an  action  on  the  develop- 


IN  PRACTICAL  MEDICINE  49 

ment  of  the  skeleton,  on  nutrition,  and  also  a  pres- 
sor or  depressor  action  on  the  circulation.  He  does 
not  attempt  the  differentiation  suggested  by  Claude 
and  Gougerot,  (13)  Gandy,  Deseglise,  and  others, 
to  determine  in  which  gland  the  hypofunction  pre- 
dominates and  which  is  essentially  responsible  for 
the  disturbance.  This  undertaking  appears  to  him 
much  too  difficult  at  present.  In  Costa's  case,  how- 
ever, the  discovery  of  the  cause  was  made  by  the 
Wassermann  test  and  antisyphilitic  treatment 
caused  a  marked  change  for  the  better. 

The  majority  of  the  serious  organic  disturbances 
of  the  ductless  glands  seem  to  be  syphilitic  in  ori- 
gin. The  case  reported  by  Costa  above  was  luetic. 
In  Maase's  case,  which  has  already  been  quoted, 
there  was  a  positive  Wassermann  reaction,  and  de 
Moraes  and  Pernambuco,  (14)  in  considering  the 
relation  of  the  pluriglandular  syndrome  associated 
with  dementia  precox  in  a  girl  of  19,  established  the 
cause  as  inherited  syphilis.  They  found  that  the 
ovaries,  thyroid,  adrenals  and  mammae  were  si- 
multaneously affected. 

The  only  reason  that  we  study  disease  is  that  we 
may  be  able  the  better  to  appreciate  its  influence 
and  satisfactorily  treat  it,  so  the  consideration  of 
pluriglandular  insufficiency  would  be  incomplete 
without  reference  to  the  treatment  of  these  condi- 
tions. 

The  natural  corollary  of  pluriglandular  insuffi- 
ciency   is    pluriglandular    therapy,    and    the    most 


50  THE  INTERNAL  SECRETIONS 

practical  consideration  of  this  subject  concerns  the 
comparatively  recent  form  of  therapeutics  which 
the  knowledge  of  the  influence  of  hypoendocrinism 
has  made  possible. 

It  is  altogether  possible  that  the  change  of  air 
ordinarily  recommended  to  convalescents  and  in- 
valids, sanatorium  treatment  and  other  hygienic 
regimens,  are  beneficial  largely  because  of  the  in- 
creased activity  of  the  secretory  capacity  of  all  the 
glandular  organs  and  it  seems  that  the  tonic  phys- 
ical measures,  such  as  hydrotherapy,  electricity, 
massage,  etc.,  are  useful  in  part  at  least  because 
they  stimulate  the  endocrine  organs  to  produce 
their  vital  messengers.  In  fact,  Nogier  (15)  has 
suggested  a  special  line  of  treatment  with  the  hope 
of  specifically  exciting  the  internal  secretory  or- 
gans by  physical  methods,  just  as  these  methods 
are  used  to  stimulate  other  functions,  thus  materi- 
ally modifying  the  conditions  due  to  hypoendocrin- 
ism. This  may  be  good,  but  to  my  mind  cannot  be 
compared  with  the  more  direct  organotherapeutic 
methods. 

The  most  natural  means  to  favor  internal  secre- 
tory activity  are  the  products  of  the  internal  secre- 
tory glands  themselves.  Hallion's  law  is  the  funda- 
mental basis  of  scientific  organotherapy.  It  is  as 
follows:  "Extracts  of  an  organ  exert  on  the  same 
organ  an  exciting  influence  which  lasts  for  a  longer 
or  shorter  time.  When  the  organ  is  insufficient,  it 
is   conceivable   that   this   influence    augments    its 


IN  PRACTICAL  MEDICINE  51 

action,  and,  when  it  is  injured,  that  it  favors  its 
restoration." 

One  of  the  most  important  statements  on  the 
hormones  is  found  in  Starling's  monograph  on 
"The  Chemical  Co-ordination  of  the  Body  Func- 
tions." (16)  This  eminent  authority  confidently 
states  his  belief  that  "if  the  mutual  control  of  the 
body  be  largely  determined  by  the  production  of 
definite  chemical  substances  in  the  blood,  the  dis- 
covery of  the  nature  of  these  substances  must  en- 
able us  to  interpose  at  any  desired  place  in  these 
functions,  and  by  this  means  to  acquire  an  absolute 
control  over  the  working  of  the  human  body.  Such 
a  control  is  the  goal  for  which  medical  science  must 
ever  strive/' 

Possibly,  the  not  infrequent  cases  of  seeming 
monoglandular  disorder  which  do  not  respond  to 
the  orthodox  treatment  whether  organotherapeutic 
or  otherwise,  might  be  more  responsive  to  our  ther- 
apeutic efforts  if  the  fact  that  pluriglandular  dis- 
ease is  much  more  common  than  monoglandular 
disease  was  considered,  and  the  administration  of 
suitably  combined  extracts  was  substituted  for  the 
present  thyroid,  pituitary,  adrenal,  ovarian  or  other 
single  extracts  which  may  seem  to  be  the  proper 
treatment. 

It  is  quite  certain  that  this  subject,  now  on  the 
verge  of  our  present  knowledge,  before  many 
years  have  passed  will  be  taken  into  careful  con- 
sideration by  the  general  practitioner  as  well  as  the 


52  THE  INTERNAL  SECRETIONS 

internist,  and  the  hormone  balance  will  be  a  factor 
which  is  more  thoroughly  appreciated.  It  is  true 
that  the  goal  referred  to  in  Starling's  quotation  is 
still  far  distant,  and  we  are  a  long  way  from  ac- 
quiring "absolute  control  over  the  working  of  the 
human  body,"  but  there  can  be  no  reasonable  deny- 
ing that  the  administration  of  certain  organic  ex- 
tracts makes  possible  a  control  over  certain  func- 
tional conditions  that  is  not  obtainable  in  any  other 
way. 

For  several  years  the  writer  has  been  studying 
the  applications  of  various  combinations  of  pluri- 
glandular extracts  in  pluriglandular  insufficiencies, 
particularly  in  the  so-called  "run-down"  condi- 
tions, where  no  easily  demonstrated  and  positive 
evidence  of  any  defective  action  of  a  gland  or  series 
of  glands  can  be  demonstrated.  Such  cases  include 
many  forms  of  neurasthenia  and  functional  neu- 
roses, and  it  is  obvious  that  in  the  majority  of  these 
cases  there  must  be  a  disturbed  endocrinism.  It  is 
hardly  reasonable  to  suppose  that  in  an  individual 
with  prominent  manifestations  of  half-speed  func- 
tion, such  as  constant  fatigue  on  slight  exertion, 
defective  oxidation  as  evidenced  by  low  urinary 
solids,  nerves  that  are  easily  set  "on  edge,"  circu- 
lation that  is  poor,  with  cold,  clammy  extremities, 
and  not  infrequently  reduced  tension  and  ambi- 
tion, and  mental  powers  much  below  par,  that  the 
production  of  the  essential  chemical  messengers  is 
not  reduced  just  as  are  all  the  body  activities.  This 


IN  PRACTICAL  MEDICINE  53 

being  the  case,  pluriglandular  therapy  not  only 
serves  to  replace,  in  however  slight  degree,  the 
missing  secretions,  but  favors  an  increased  produc- 
tion of  them  by  the  homostimulant  action  already 
referred  to. 

Theoretically  this  sounds  very  plausible  and 
practically  it  has  been  found  to  work  very  nicely. 
Pluriglandular  therapy  is  undoubtedly  empirical, 
for  in  the  class  of  cases  under  discussion  at  least, 
there  is  no  definite  proof  as  to  which  of  the  duct- 
less glands  is  deficient  and  to  what  extent.  For 
this  reason  it  has  been  ridiculed  by  some  who  for- 
get that  nine-tenths  of  our  present  therapeutics 
was  at  one  time  purely  empirical,  while  a  good 
share  of  it  still  has  no  positive  scientific  basis.  A 
procedure  that  has  secured  results  before  may  do 
so  again,  hence  it  is  worth  trying.  This  is  the  pres- 
ent position  of  pluriglandular  therapy,  and  it  is  be- 
lieved that  the  successes  already  obtained  are  an 
earnest  of  what  is  in  prospect. 

Several  combinations  of  organic  extracts  have 
been  tried  experimentally,  and  from  a  considerable 
experience  it  seems  that  the  really  tonic  principles 
of  this  character  are  to  be  secured  from  the  pitui- 
tary body,  thyroid  and  gonads.  My  experience  has 
been  limited  to  the  use  of  combinations  of  the  ex- 
tracts of  the  ductless  glands  which  are  known  to 
have  a  tonic  effect.  Chief  among  these  are  the  thy- 
roid, posterior  lobe  of  the  pituitary  and  gonads,  and 
for  the  past  two  years  I  have  used  a  preparation 


54  THE  INTERNAL  SECRETIONS 

called  hormotone  with  excellent  results  in  a  variety 
of  "run-down"  states,  in  some  of  which  there  were 
obvious  disturbances  of  one  or  more  of  the  ductless 
glands  and  in  others  in  which  this  change  was  pre- 
sumed to  be  present  though  not  so  evident  from  a 
clinical  standpoint. 

Leonard  Williams,  whose  studies  in  this  field  are 
of  considerable  interest,  reported  to  the  therapeu- 
tical section  of  the  Royal  Society  of  Medicine  (17) 
that  he  had  found  that  while  pituitary  substance 
had  given  good  results  in  those  "curious  and  indefi- 
nite conditions — neurotic  or  neurasthenic — which 
occur  so  frequently  in  moth-eaten  maiden  ladies 
who  emerge  from  boarding  houses  to  go  to  church 
— I  do  not  know  how  it  does  it,  but  it  makes  them 
feel  better — .  .  .  .  Since  I  have  been  using  a 
mitrailleuse  called  hormotone  I  have  had  consider- 
able success  in  those  cases  just  referred  to  as  bene- 
fited by  pituitary."  Among  the  conditions  which 
I  have  treated  are  neurasthenia  (in  men  and  wom- 
en), amenorrhea,  sexual  neuroses  and  impotence, 
as  well  as  several  cases  in  which  the  manifestations 
were  not  sufficiently  marked  to  be  definitely  named 
— the  "run-down"  conditions. 

This  treatment  is  by  no  means  a  specific,  and  my 
percentage  of  good  results  is  only  between  60  per 
cent,  and  70  per  cent.  I  have  seen  no  really  bad 
effects,  the  only  untoward  effects  occasionally 
noted  being  a  feeling  of  irritability  and  temporarily 
increased  nervousness,  which  disappeared    on    re- 


IN  PRACTICAL  MEDICINE  55 

ducing  the  dose  of  hormotone  and  did  not  reappear 
when  its  administration  was  very  gradually  in- 
creased. 

In  senile  conditions  and  old  age  there  is  an  in- 
variable pluriglandular  insufficiency  due  to  the  pro- 
gressive decline  in  all  the  functions.  Lorand,  whose 
book  on  this  subject  (18)  is  practical  as  well  as  in- 
teresting, makes  frequent  reference  to  the  value  of 
organotherapy,  and  I  must  admit  that,  in  a  number 
of  cases  which  have  come  to  my  attention,  the  com- 
bination previously  referred  to  has  seemed  to  re- 
kindle the  vital  fires. 

The  advantages  of  pluriglandular  therapy  are 
essentially  the  advantages  to  be  derived  from  the 
individual  substances  which  are  combined.  Obvi- 
ously such  combinations  are  made  with  their  syner- 
gistic action  in  mind.  I  have  personally  used  small 
doses  of  antagonizing  extracts  with  good  results, 
because  it  seems  that  each  of  the  substances  stimu- 
lates the  corresponding  organs,  thus  increasing  the 
hormone  content  of  the  blood  as  a  whole  and 
strengthening  the  chemical  messages  which  are  of 
such  vital  importance.  A  point  worth  emphasis 
concerns  the  capacity  of  the  individual  organ  to  re- 
spond to  the  stimulus  of  the  corresponding  extract. 
It  seems  established  that  "the  degree  of  stimulation 
exerted  by  the  administration  of  the  hormone-bear- 
ing substances  is  in  direct  ratio  to  the  need  for  such 
stimulation,  i.  e.,  an  extract  is  more  efficient  when 
a  corresponding  active  principle  is  deficient  in  the 


56  THE  INTERNAL  SECRETIONS 

body  than  when  present  in  normal  amounts.  Hence 
in  a  combination  of  several  extracts  the  principal 
action  is  the  one  which  is  deficient;  that  is  to  say, 
the  more  it  is  needed,  the  more  useful  it  is."  (19) 

Before  closing  it  is  proper  to  mention  several  re- 
ports in  the  literature  on  various  forms  of  pluri- 
glandular therapy.  In  addition  to  the  treatment 
of  the  definite  thyro-pituitary  deficiencies  with  thy- 
rodi  and  pituitary  extracts,  as  first  suggested  by 
Renon  and  Delille,  (20)  Starkey  (21)  has  been 
treating  certain  nervous  diseases  with  a  combina- 
tion of  thyroid,  parathyroid,  testis  and  ovary. 

In  gynecological  practice  it  is  not  uncommon  to 
combine  lutein  with  small  doses  of  thyroid  with 
advantage  in  conditions  where  lutein  may  be  indi- 
cated. A  combination  of  several  extracts  is  given 
by  McCready  in  children  with  defective  endocrine 
development  and  it  seems  quite  well  established 
that  combinations  are  more  useful  than  single 
gland  extracts — at  least  in  this  class  of  cases. 

Bazzochi  (22)  has  used  a  combination  of  thyroid, 
thymus  and  spleen  in  pyloric  cancer.  In  pharyn- 
geal carcinoma,  Shirlaw  (23)  suggests  the  use  of 
the  preparation  called  "Tabloid  three  glands,"  each 
tablet  containing  a  large  dose  of  thyroid  (6  grains) 
with  the  addition  of  small  doses  of  adrenal  and 
pituitary  substances.  Unquestionably  in  cancer 
there  is  a  definite  hypoendocrinism,  and  attempts 
to  modify  this,  while  possibly  without  specific  ef- 
fect upon  the  cancer  itself,  may  be  of  assistance  in 


IN  PRACTICAL  MEDICINE  57 

modifying  other  conditions  which  cause  inconveni- 
ence to  the  patient.  "Cancer  is  essentially  a  dis- 
ease of  nutrition — i.  e.,  errors  in  nutrition,  whether 
local  or  general,  are  the  factors  which  permit  of 
the  implantation  of  cancer  cells  and  the  growth  of 
the  tumor.  The  ductless  glands  preside  over  nu- 
trition. Hence  it  is  not  unreasonable  to  suppose 
that  there  may  be  some  relation  between  disturb- 
ances of  the  hormone  balance  and  cancer,  and,  too, 
that  there  may  be  some  prospect  of  therapeutic 
value  in  the  treatment  of  this  disease  by  organo- 
therapy." (24)  Finally,  Billard  (25)  has  advocated 
a  combination  of  the  extracts  of  spleen,  liver  and 
pancreas  as  an  adjunct  remedy  of  possible  helpful- 
ness in  cancer. 

Altogether  the  possibilities  of  various  pluri- 
glandular combinations  are  almost  without  num- 
ber, since,  as  Leonard  Williams  (17)  has  indicated, 
the  mitrailleuse  is  seemingly  more  useful  than  the 
single  rifle  shot. 

Since  this  was  written  Little  (26)  has  made  an- 
other interesting  communication  on  his  study  of 
cancer,  and  shows  that  not  only  must  we  consider 
the  relation  of  the  ductless  glands  and  their  dis- 
orders to  cancer,  but  that  the  use  of  certain  prod- 
ucts of  these  organs  has  a  decided  effect  in  favor- 
ing the  response  of  the  body  to  other  treatment. 
He  used  extracts  of  the  pancreas  and  adrenal  cor- 
tex. Little's  hypothesis  has  several  important 
points  which  are  worthy  of  repetition:    The  prob- 


58  THE  INTERNAL  SECRETIONS 

able  origin  of  the  growth  is  in  a  highly  specialized 
cell  or  cells,  which  for  some  reason  or  other  have 
undergone  a  retrograde  metamorphosis  to  the 
point  where  the  power  of  reproduction,  common 
originally  to  all  cells  but  lost  in  these  highly  spe- 
cialized cells,  has  reappeared.  This  reproduction 
of  such  reverted  cells  is  caused  by  a  relative  hypo- 
function  of  certain  ductless  glands.  The  ductless 
glands  at  fault  in  each  case  have  some  vital  relation 
to  sugar  metabolism  or  calcium  metabolism  or 
both. 


It  is  over  two  years  and  a  half  since  the  fore- 
going was  prepared,  and  in  that  time  I  have  had 
numerous  opportunities  to  see  how  important  is 
the  appreciation  of  pluriglandular  conditions. 
Nothing  establishes  one's  faith  in  medicine,  or  any 
part  of  it,  like  clinical  success.  So  I  will  amplify 
this  chapter  with  two  brief  case  reports,  one  with 
which  I  had  to  do  personally  and  the  other  to 
which  my  attention  was  drawn  by  the  late  Dr. 
Wendell  Reber  of  Philadelphia. 

When  my  address  was  given  before  the  Riverside 
County  Medical  Society*  Dr.  D.  C.  Strong  of  San 
Bernardino,  reported  a  case  of  pituitary  cyst  in  a 
boy.  This  had  been  successfully  punctured  and  de- 
compressed and  the  boy  recovered  from  the  neigh- 
borhood and  pressure  symptoms  and  was  given 
pituitary  gland  with  additional  improvement.  How- 


*See  Chapter  IV. 


IN  PRACTICAL  MEDICINE  59 

ever  this  did  not  last,  and  the  lad's  mentality  and 
progress  was  about  at  a  standstill  when  I  heard  of 
the  circumstances.  Naturally  defective  mentality 
reminds  one  of  thyroid  trouble,  despite  the  proven 
pituitary  disease,  and  I  suggested  that  the  pituitary 
feeding  be  continued  and  reinforced  with  the  addi- 
tion of  thyroid  gland.  This  was  done  with  astound- 
ing results,  for  the  boy  is  now  as  bright  as  any  of 
his  schoolmates  and  an  excellent  student.  Here, 
of  course,  the  pituitary  insufficiency  was  but  a  part 
of  the  complex,  and  the  pluriglandular  therapy  was 
much  more  successful  than  the  administration  of 
the  single  gland  alone. 

The  other  case  was  just  as  peculiar.  Dr.  Reber 
wrote  me  of  this  and  has  since  reported  the  case  in 
the  New  York  Medical  Journal  (1915,  ci,  392). 
A  man  came  for  treatment  for  a  progressive  blind- 
ness and  for  some  reason  or  another  was  given  thy- 
roid gland  with  no  perceptible  benefit.  He  then 
received  pituitary  gland  in  conjunction  with  the 
thyroid,  with  considerable  benefit  to  his  vision. 
Some  time  later  the  vision  was  again  impaired  and 
pituitary  gland  was  given  since  it  had  been  so  ef- 
fective previously.  It  was  a  failure  until  it  was  re- 
called that  he  had  taken  both  thyroid  and  pituitary, 
and  thyroid  was  added.  The  benefit  was  as  prompt 
as  previously,  thus  giving  fairly  substantial  evi- 
dence that  thyroid  alone  and  pituitary  alone  were 
practically  inactive;  but  that  the  combination 
caused  a  change  in  conditions  which  allowed  of  a 


60  THE  INTERNAL  SECRETIONS 

re-establishment  of  the  disorder  under  treatment. 

I  am  confident  from  many  clinical  experiences 
that  cases  in  which,  say,  thyroid  treatment  is  obvi- 
ously indicated,  often  will  respond  more  satisfac- 
torily when  further  search  is  made  for  associated 
endocrine  disorder  and  suitable  pluriglandular 
medication  is  substituted. 

REFERENCES 

1.  Editorial:  "The  Clinical  Relations  of  the  Internal 
Secretions,"  New  York  Med.  Jour.,  1912,  ii,  1183. 

2.  "L'Endocrinologia  nelle  sue  Cliniche  Applicazioni," 
Clin.  Med.  Ital.,  Rome,  1913,  Hi,  599;  see  also  Ibid.,  1912, 
li,  665. 

3.  Holmes,  B. :  "The  Glands  of  Internal  Secretions/' 
Lancet-Clinic,  Cincinnati,  1914,  cxii,  319. 

4.  Mullaly,  E.  J. :  "A  Case  Illustrating  Ductless  Gland 
Relationship,"  Can.  Med.  Assoc.  Jour.,  Toronto,  1914,  iv,  37. 

5.  Campbell,  H. :  "The  Role  of  the  Blood-Plasma  in 
Disease,"  Lancet,  London,  1907,  i,  313  et  seq. 

6.  Editorial  note :  "A  Unique  Case  of  Pluriglandular 
Insufficiency,"  Med.  Record,  New  York,  1914,  lxxxv,  301. 

7.  Consolazio,  E. :  "Sindromi  Plurighiandolari,"  Gaz. 
Inter,  d.  med.,  Naples,  1914,  xvii,  568. 

8.  Bianchi,  G. :  "Osservazioni  Istopatologiche  su  un 
Caso  di  Insufficienza  Plurighiandolare  Endocrina,"  Pathol., 
Genoa,  1914,  vi,  74. 

9.  Zilocchi,  A. :  "Importanza  Patogenetica  de  TAppa- 
recchio  Plurighiandolare,"  II  Morgagni,  Milan,  1913,  lx,  352- 
361. 

10.  Costa,  S. :  "Syndrome  d'lnsuffisance  Pluriglandu- 
laire,"  Paris  Med.,  1913,  xi,  378. 

11.  Rebattu,  M. :  "Syndrome  Pluriglandulaire  (Geni- 
to-Surreno-Thyroidien),"  Lyon  Med.,  Lyons,  1914,  cxxii, 
605. 

12.  Parhon,  C.  et  al. :  "Note  sur  les  Syndromes  Pluri- 
glandulaires  experimentaux,"  Rev.  Neurol.,  Paris,  1913, 
xxvi,  226. 


IN  PRACTICAL  MEDICINE  61 

13.  Claude,  H.,  and  Gougerot,  H. :  "Syndromes  Pluri- 
glandulaires :  Delimitation  des  Syndromes  d'insuffisance  et 
d'hyperfonctionnement  Pluriglandulaires,"  Gaz.  d.  Hop., 
Paris,  1912,  lxxxv,  849-897. 

14.  de  Moraes,  P.  V.,  and  Pernambuco,  P. :  "Consid- 
erations regarding-  a  Case  of  Pluriglandular  Syndrome  as- 
sociated with  Dementia  Precox,"  Arch,  Brasileiros  de  Med., 
Rio.,  1912,  ii,  671. 

15.  Nogier,  Ph.:  "L'excitation  et  la  Frenation  des 
Glandes  Endocrines  par  les  Procedes  Physiques,"  Bull,  de 
l'Acad.  Sci.,  Paris,  1912. 

16.  Starling,  E.  H. :  ''The  Chemical  Co-ordination  of 
the  Activities  of  the  Body,"  Science  Progr.,  London,  1906- 
7,  i,  557. 

17.  Williams,  L. :  "Discussion  on  the  Therapeutic 
Value  of  Hormones,"  Proc.  Roy.  Soc.  Med.  (Sec.  Ther.), 
London,  1914,  vii,  33. 

18.  Lorand,  A.:  Old  Age  Deferred,  1911,  F.  A.  Davis 
Co.,  Philadelphia. 

19.  Harrower,  H.  R. :  Practical  Hormone  Therapy, 
1914,  Bailliere,  London,  p.  424. 

20.  Renon,  L.,  and  Delille,  A. :  "Sur  les  eflets  des 
extraits  d'hypophyse,  de  thyroide,  de  surrenale,  d'ovaire 
employes  en  injections  intraperitoneales  (simples  et  com- 
bines) chez  le  lapin,"  C.  r.  Soc.  Biol.,  Paris,  1908,  lx,  1037. 

21.  Starkey,  F.  R. :  "The  Combined  use  of  Thyro- 
parathyroid,  Pituitary,  Ovarian,  and  Testicular  Extracts," 
N.  Y.  Med.  Jour.,  1112,  xcv,  1257. 

22.  Bazzochi,  A. :  "Sulla  Istoterapia  del  Tumori 
Maligni  dell'  uomo,"  Tumori,  Rome,  1913,  iii,  320. 

23.  Shirlaw,  J.  T. :  "The  Nature  and  Origin  of  Can- 
cer," Brit.  Med.  Jour.,  London,  1911,  ii,  1625;  see  also 
L'pool  Med.-Chir.  Jour.,  1913,  xxxiii,  398. 

24.  Harrower,  H.  R. :  Practical  Hormone  Therapy, 
1914,  Bailliere,  London,  p.  422. 

25.  Billard,  M. :  "Essai  d'opotherapie  Anticancereuse," 
Centre  med.  et  pharm.  (Gannat),  1909,  xiv,  319. 

26.  Little,  S.  W.:  "A  Further  Study  of  Cancer,"  Bos- 
ton Med.  and  Surg.  Jour.,  1914,  clxxi,  587. 


VI 

SHELL   SHOCK  ("NEURASTHENIA")    AND 

THE  INTERNAL  SECRETIONS:  WITH 

SUGGESTIONS  AS  TO  TREATMENT 

THERE  seems  to  be  reliable  evidence,  both  phy- 
siological and  clinical,  that  the  severe  nervous  dis- 
organization not  infrequently  following  a  period  of 
trench  warfare,  is  either  directly  due  to  a  disturb- 
ance in  the  work  the  glands  of  internal  secretion, 
or  at  least  is  complicated  by  a  glandular  dyscrasia 
or  dyshormonism  (dyscrinism). 

The  writer  has  had  no  opportunity  to  see  cases 
of  this  character,  but  several  reports  from  corre- 
spondents on  war  service  have  aroused  an  interest 
in  this  subject,  which  has  lead  to  a  study  of  its  lit- 
erature and  a  comparison  of  this  with  the  writer's 
personal  observations. 

The  excellent  work  of  T.  R.  Elliott,  (1)  of  Lon- 
don, followed  by  the  comprehensive  series  of  ex- 
periments by  Cannon,  (2)  of  Harvard,  has  quite 
definitely  determined  a  relation  between  the  ad- 
renal system  and  the  sympathetic  nervous  system. 
It  is  now  understood  that  those  factors  which  act 
upon  and  through  the  sympathetic  nervous  system 


Reprinted  from  "The  Prescriber,"  Edinburgh,  October,  1916. 

NOTE:  The  editor  of  "The  Prescriber,"  who  is  a  personal 
friend  of  the  writer,  submitted  certain  clinical  notes  and  sugges- 
tions, and  at  the  same  time  asked  for  an  article  outlining  some 
sort  of  a  feasible  explanation  of  the  possible  relation  of  the  endo- 
crine glands  to  shell  shock.  This  is  merely  an  attempt  to  relate 
these. 

(62) 


IN  PRACTICAL  MEDICINE  63 

also  influence  the  adrenals;  and  that  the  sympa- 
thetic manifestations  resulting  from  pain,  rage, 
fear,  hunger,  and  the  emotions  cause  a  decided 
stimulation  of  the  adrenals  with  an  immediate  pro- 
duction of  a  greatly  augmented  supply  of  adrenin 
to  the  circulating  blood.  This  is  followed,  at  a 
longer  or  shorter  period,  by  an  equally  well  defined 
adrenal  depletion  or  hypoadrenia,  accompanied  by 
just  such  clinical  manifestations  as  we  expect  to 
find  in  shock — vasomotor  irritability  and  instabil- 
ity, hypotension,  insomnia,  depression,  and  an  ex- 
tremely well  marked  asthenia.  This  last  symptom 
is  the  typical  accompaniment  of  adrenal  disease 
(Addison),  and  almost  invariably  complicates  the 
syndrome  of  pluriglandular  insufficiency  (hypo- 
crinism). 

This  condition  of  hypoadrenia  is  not  uncommon 
in  consulting  work,  and  complicates  many  more 
cases  than  one  might  expect.  Crile's  "anoci-asso- 
ciation"  is  nothing  more  nor  less  than  an  attempt 
to  forestall  just  such  a  condition  by  the  removal  as 
far  as  possible  of  circumstances  known  to  cause  ad- 
renal excitation  prior  to  operation.  Sajous  has  long 
emphasized  the  importance  of  "terminal  hypoad- 
renia," while  Sergent,  of  Paris,  has  written  many 
an  article  upon  'Tinsuffisance  surrenale."  These 
contributions  more  than  convince  one  that  this 
endocrine  syndrome  is  quite  common. 

Judging  from  the  foregoing  physiological  facts, 
"one  can  quite  easily  understand  that  just  such  a 


64  THE  INTERNAL  SECRETIONS 

condition  would  be  present  in  individuals  driven 
from  home  and  subjected  to  exposure  and  hunger. 
Similarly,  men  returning  from  the  trenches,  where 
they  have  been  subject  to  extreme  fatigue  and  the 
tenseness  of  the  atmosphere,  as  well  as  the  mental 
effects  of  losing  their  comrades  and  themselves  suf- 
fering from  wounds  and  shocks,  must  also  be  con- 
sidered to  be  in  a  state  of  adrenal  insufficiency."  (3) 
This  condition  of  hypoadrenia  was  a  prominent 
factor  in  the  "vivisection  of  a  nation,"  so  well  ex- 
plained by  Crile  in  an  address  delivered  at  the 
American  Ambulance  at  Neuilly,  during  his  service 
in  France.  (4) 

Elliot  Smith,  (5)  of  Manchester,  after  carefully 
considering  the  incidence  and  causation  of  shock  in 
soldiers,  intimates  that  mental  instability  is  the 
most  common  groundwork  for  the  superimposition 
of  this  condition.  His  position  may  be  summed  up 
in  his  own  words:  "The  real  trauma  is  psychical, 
not  physical. "  While  it  is  impossible  to  deny  that 
the  impressions  upon  the  mind  are  both  decided 
and  influential,  there  must  also  be  a  physical  factor 
in  many  of  these  cases. 

This  subject  was  recently  referred  to  by  Renon 
(6)  in  a  paper  read  before  the  Societe  de  Thera- 
peutique,  Paris,  and  the  symptom  complex  which 
he  describes  as  due  to  l'angoisse  de  guerre  is  almost 
typical  of  dyshormonism,  and  especially  that  form 
in  which  hypoadrenia  is  well  marked.    Renon  finds 


IN  PRACTICAL  MEDICINE  65 

that  a  neuropathic  or  arthropathic  physical  sub- 
stratum is  common  in  individuals  subject  to  the 
more  marked  effects  of  "war  shock, "  and  that  the 
use  of  alcohol  is  a  pronounced  predisposing  factor. 

Among  the  usual  symptoms  enumerated  by 
Renon  as  being  due  to  this  "war  neurasthenia"  are 
several  which  can  be  quickly  connected  with  the 
endocrine  organs.  A  progressive  loss  of  weight  is 
the  rule — the  glands  of  internal  secretion  control 
both  nutrition  and  growth;  the  temperament  is 
changed  and  the  disposition  becomes  uncertain — 
mental  stability  and  activity  are  commonly  con- 
nected with  ductless  glandular  dyscrasias;  arterial 
tension  is  reduced — common  both  in  pluriglandular 
insufficiency  and  in  hypoadrenia;  dermography  is 
reported  to  be  nearly  always  present — one  of  the 
typical  manifestations  of  severe  adrenal  depletion 
is  the  dermographic  sign  first  mentioned  by  Ser- 
gent,  and  called  by  him  la  ligne  blanche  surrenale. 
I  cannot  but  believe  that  the  most  constant  single 
factor,  and  one  that  is  quite  susceptible  to  treat- 
ment, in  "shell  shock"  or  "war  neurasthenia,"  is 
pluriglandular  insufficiency. 

That  this  conception  of  the  relation  of  neuras- 
thenia to  the  internal  secretions  is  coming  to  be 
more  generally  accepted  may  be  noted  from  a  re- 
cent editorial  in  the  Journal  of  the  American  Medi- 
cal Association,  (7)  which  comments  favorably 
upon  a  paper  by  T.  A.  Williams,  (8)  of  Washing- 
ton, describing  the  disorder  as  a  syndrome  of  ad- 


66  THE  INTERNAL  SECRETIONS 

renal  insufficiency.  Williams  very  aptly  remarks 
that  the  term  "neurasthenia"  is  only  a  "convenient 
cloak  for  failure  to  investigate  the  case  sufficiently/' 
and  that  there  must  be  some  tangible  cause.  He 
concludes  that  many  patients  who  show  symptoms 
of  neurasthenia  with  low  blood  pressure,  loss  of 
mental  elasticity,  mental  and  physical  depression, 
and  who  tell  of  having  "lost  their  nerve,"  are  very 
frequently  suffering  from  adrenal  insufficiency.  He 
has  given  dried  adrenal  substance  in  such  cases, 
and  has  noted  improvement  in  many  of  them. 

Corbett,  of  Minneapolis,  (9)  finds  that  adrenin 
insufficiency  is  a  prominent  factor  in  shock;  he 
does  not  maintain  that  its  loss  is  shock,  but  rather 
that  adrenin  is  necessary  to  overcome  shock,  and 
any  factors  which  deplete  its  supply  favor  the  de- 
velopment of  that  condition.  Symptoms  of  shock 
fully  develop  only  after  the  adrenals  are  greatly 
exhausted,  and  symptoms  of  it  become  extreme  the 
more  marked  is  this  adrenal  depletion.  He  con- 
cludes that  shock  is  a  composite  in  which  adrenin 
exhaustion  and  oligemia  are  predominant  factors. 
Anesthesia,  pain,  fright,  and  trauma  are  immediate 
agents  in  producing  adrenin  exhaustion  as  well  as 
shock. 

Sir  James  Mackenzie  (10)  asserts  his  belief  that 
at  least  90  per  cent,  of  the  cases  of  "soldier's  heart" 
that  have  been  certified  and  treated  as  cardiac  affec- 
tions are  not  primarily  heart  cases  at  all,  and  that 
the  principles  of  treatment  applicable  in  such  cases 


IN  PRACTICAL  MEDICINE  67 

differ  widely  from  those  for  the  control  of  heart 
failure.  The  symptoms  enumerated  by  Mackenzie 
are  quite  similar  to  those  mentioned  previously  as 
being  expected  to  follow  hypocrinism  and,  espe- 
cially, severe  adrenal  exhaustion.  He  mentions  a 
sense  of  fatigue  or  exhaustion  easily  induced  as  be- 
ing common  to  all — the  typical  "endocrine  asthe- 
nia" already  noted  several  times.  The  heart's  rate 
is  often  not  increased,  but  in  some  it  is  persistently 
increased,  as  high  as  120  per  minute — a  condition 
commonly  associated  with  dysthyroidism.  The 
mental  condition  is  somewhat  varied,  periods  of  de- 
pression are  not  infrequent,  and  patients  are  often 
very  irritable — both  connected  with  dysthyroidism 
or,  still  more  commonly,  with  dyscrinism. 

Mackenzie  urges  that  the  main  principles  of 
treatment  of  this  heart  disturbance  should  be  de- 
voted to  increasing  the  health  of  the  body  as  a 
whole,  so  as  to  increase  the  natural  resistance  to  in- 
fection, to  eliminate  toxic  influences,  and  to  brace 
up  the  whole  man  bodily  and  mentally.  To  achieve 
this,  Mackenzie  recommends  fresh  air  and  judi- 
cious exercise.  While  these  are  doubtless  most  im- 
portant measures,  it  must  be  remembered  that  re- 
sistance to  infection  is  largely  the  concern  of  the 
thyroid  gland,  while  the  principal  detoxicating 
agencies  in  the  body  are  theJiver,  the  thyroid,  and 
the  adrenals.  In  the  matter  of  treatment,  there- 
fore, it  is  only  rational  that  these  organs  should  be 
studied  and,  where  advisable,  suitably  stimulated. 


68  THE  INTERNAL  SECRETIONS 

From  what  has  preceded  it  will  appear  that  medi- 
cation calculated  to  stimulate  the  adrenal  system 
may  be  helpful  in  cases  of  shell  shock  or  neuras- 
thenia; and  doubtless  it  is,  especially  if  used  in  the 
manner  suggested  by  Tom  Williams,  i.  e.,  desic- 
cated adrenal  gland  by  mouth.  Sergent  has  been 
using  this  form  of  treatment  in  France,  (11)  and 
finds  it  of  exceptional  value  in  the  severe  cases 
where  the  signs  of  acute  adrenal  exhaustion  are 
elicited.  Here  hypodermic  injections  of  adrenalin 
solution,  from  15  to  as  high  as  30  minims  at  suit- 
able intervals,  have  undoubtedly  saved  life. 

In  the  course  of  the  discussion  of  Corbett's  pa- 
per, (9)  mentioned  previously,  one  physician  asked 
why,  if  these  symptoms  are  due  to  adrenal  insuffi- 
ciency, cannot  they  be  relieved  by  the  administra- 
tion of  adrenalin.  In  his  reply  Corbett  said  he  did 
not  think  that  adrenalin,  administered  artificially, 
was  the  antidote  for  shock,  because  the  amounts  of 
adrenalin  normally  in  the  blood  are  exceedingly 
small,  and  if  an  attempt  were  made  to  maintain  the 
blood  pressure  by  forcing  adrenalin,  continued 
larger  doses  would  have  to  be  used  to  maintain  the 
results.  Such  continued  and  increasing  dosage 
would  have  a  deleterious  effect  upon  the  blood  ves- 
sels, and  might  increase  the  concentration  of  the 
blood,  adding  this  factor  to  the  shock.  I  am  not 
sure  about  this  effect  of  adrenalin  on  the  vessels, 
but  I  do  know  that  pituitary  preparations  are 
much  more  effective  than  adrenalin  in  the  immedi- 


IN  PRACTICAL  MEDICINE  69 

ate  treatment  of  shock  and  collapse,  their  influence 
is  more  prolonged,  untoward  by-effects,  as  rigors, 
coldness,  palpitation,  etc.,  are  less  likely  to  follow, 
and  the  general  influence  upon  other  functions,  as 
diuresis,  intestinal  peristalsis,  etc.,  are  both  salu- 
tary and  desirable.  Hence  recourse  to  posterior 
pituitary  preparations  is  now  almost  the  rule  in  the 
immediate  treatment  of  shock,  though  there  are  un- 
doubtedly cases  of  severe  hypoadrenia,  such  as 
those  mentioned  by  Sergent,  Sajous,  Josue  and 
others,  in  which  a  dose  of  adrenalin  might  give  bet- 
ter results. 

The  use  of  one  or  the  other  of  these  hormone 
preparations  in  cases  of  this  character  is  rational; 
but  they  are  not  quite  suitable  measures  for  the 
control  of  the  chronic,  unyielding,  and  persistent 
syndromes  which  outlast  the  actual  collapse,  and 
we  must  look  elsewhere  for  help. 

Fortunately  we  have  other  endocrine  glands 
which  are  so  intimate  with  the  adrenals  as  to  be 
classified  by  some  as  a  part  of  the  "adrenal  system," 
and  from  them  we  can  draw  in  the  hope  of  gaining 
results  in  this  class  of  disorders.  The  thyroid,  pitu- 
itary, and  gonads  all  contain  principles  that  are 
valuable  here.  Combinations  of  these  have  been 
used  for  some  years  with  good  results.  The  marked 
advantage  of  pituitary,  for-instance,  over  adrenal 
substance  is  that  it  contains  a  more  stable  and 
therapeutically  lasting  principle,  and,  without  go- 
ing into  details,  its  influence  upon  the  vascular  and 


70  THE  INTERNAL  SECRETIONS 

muscular  tone  seems  to  be  much  better  than  that 
resulting  from  adrenal  therapy. 

The  stimulating  effect  of  small  doses  of  thyroid 
extract  is  not  confined  to  cases  with  obvious  hypo- 
thyroidism. As  a  matter  of  fact,  this  influence  upon 
the  adrenals  is  well  marked.  Sajous,  Schafer,  and 
others  have  directed  attention  to  the  close  histo- 
logical and  physiological  analogy  which  exists  be- 
tween the  interstitial  cells  of  the  gonads  and  the 
corresponding  cells  in  the  adrenals.  There  seems 
to  be  a  rational  as  well  as  an  empirical  basis  for 
pluriglandular  therapy;  for  one  is  thus  following 
Nature's  own  method  by  giving  a  mixture  of  sev- 
eral useful  principles.*  Further  than  this,  the  vari- 
ous cell  units  of  the  body  have  accustomed  them- 
selves to  selecting  those  chemical  messengers 
which  they  stand  most  in  need  of  (the  blood  is  a 
solution  of  unnumbered  chemical  substances)  ;  con- 
sequently, when  we  give  several  organotherapeutic 
extracts  combined,  the  influence  that  may  be  ex- 
pected to  predominate  is  the  result  of  the  action  of 
that  hormone  which  is  most  needed,  and  for  which 
certain  cells  are  seeking  in  vain,  simply  because  the 
organ  producing  it  has  been  played  out. 

Another  reason  for  giving  mixed  gland  extracts 
lies  in  the  fact  that  all  these  endocrine  organs  are 
so  intimate  with  one  another  that  disturbance  in 
one  invariably  causes  changes  in  the  work  of  the 


♦Just  as  we  use  combinations  of  the  four  food  elements  and 
expect  the  body  to  make  use  of  each  where  it  is  needed  most. 


IN  PRACTICAL  MEDICINE  71 

other  glands  upon  which  the  first  affected  gland  is 
dependent.  According  to  Bayard  Holmes,  (12)  of 
Chicago,  evidence  has  accumulated  to  show  that 
disease  of  the  ductless  glands  is  usually  plural 
rather  than  isolated  and  single.  "Pluriglandular 
disease  is  rather  the  rule  than  the  exception — the 
use  of  gland  extracts  in  the  treatment  of  aplasias  of 
the  pluriglandular  system  has  become  an  estab- 
lished therapeutic  measure  of  miraculous  potency." 

From  a  clinical  standpoint  I  have  had  occasion  to 
use  a  preparation  called  Hormotone  in  a  number 
of  cases  "knocked  out"  by  combinations  of  circum- 
stances other  than  those  related  to  trench  warfare. 
I  have  found  it  useful  in  various  forms  of  neuroses 
due  to  toxemia  or  severe  mental  strain,  and  in  sev- 
eral of  the  gynecological  troubles  in  which  there 
is  a  well  defined  dyshormonism.  This  preparation 
contains  the  so-called  "dynamogenic"  hormones 
from  the  glands  which  exert  their  principal  effects 
on  the  adrenal  system:  these  are  the  thyroid,  pitu- 
itary, and  gonads.  Small  doses  of  these  extracts 
are  useful  in  the  adjunct  treatment  of  just  such 
cases  as  have  been  outlined  in  this  article.  I  have 
had  several  most  interesting  experiences  reported 
to  me  from  Europe,  and  since  they  will  form  a  fit- 
ting climax  to  this  communication,  a  resume  of 
them  will  be  given. 

At  a  hospital  in five  cases  of  "trench  neuras- 
thenia" were  treated  for  some  weeks  with  from 
2y2  to  7y2  grains  of  this  preparation  three  times  a 


72  THE  INTERNAL  SECRETIONS 

day,  in  addition,  of  course,  to  the  usual  expectant 
treatment.  Their  wounds  had  all  healed,  but  the 
shock  was  still  prominent,  and  tachycardia,  tre- 
mors, and  depression  were  present.  All  suffered 
more  or  less  from  insomnia.  Two  weeks  of  this 
treatment  enabled  two  to  be  discharged  "fit  for 
service,''  despite  the  fact  that  they  had  been  under 
treatment  "for  weeks  and  months  with  no  percep- 
tible improvement."  The  other  three  grew  better, 
but  did  not  respond  so  rapidly. 

Another  report  mentions  the  use  of  this  prepara- 
tion in  several  soldiers  home  from  the  Dardanelles 
with  the  usual  after-effects  of  severe  dysentery  and 
nervous  shock.  (By  the  way,  it  has  been  well  estab- 
lished that  dysentery  is  a  most  common  cause  of 
hypoadrenia,  while  some  believe  that  the  algid 
stage  of  this  disease,  and  of  cholera,  is  essentiallv 
an  acute  adrenal  exhaustion.)  Hormotone  evi- 
dently assisted  in  the  re-establishment  of  the  nor- 
mal "balance,"  the  appetite  increased,  and  it  was 
possible  for  these  soldiers  to  sleep  quietly  and  rest- 
fully.  It  was  also  remarked  that  they  lost  the  feel- 
ing of  depression,  which,  after  all,  is  one  of  the 
most  serious  and  persistent  of  the  symptoms  of 
this  disorder. 

In  France  the  practice  of  "opotherapie"  has 
reached  a  much  more  advanced  stage  than  in  Eng- 
land or  America.  Pluriglandular  therapy  is  fairly 
well  established  there,  and  there  should  be  no  rea- 
son why  the  results  could  not  be  duplicated  any- 


IN  PRACTICAL  MEDICINE  73 

where.  In  Germany,  too,  this  subject  has  not  been 
overlooked,  although  the  German  literature  has  al- 
ways evidenced  a  paucity  of  information  on  organo- 
therapy, most  of  the  real  advances  in  this  line  hav- 
ing emanated  from  other  countries.  Thyroid  was 
introduced  by  George  Murray,  of  Manchester; 
pituitary  medication  by  Blair  Bell,  of  Liverpool ; 
parathyroid  treatment  by  Vassale,  of  Turin,  and 
Berkeley,  of  New  York;  adrenalin,  as  all  know, 
originated  in  the  investigations  of  Aldrich  and 
Takamine ;  the  corpus  luteum  was  first  studied  in 
France;  Brown-Sequard,  of  Paris,  is  the  "father  of 
scientific  organo-therapy" ;  hepatic  opotherapy  was 
first  used  by  Gilbert  and  Carnot,  of  Paris,  etc.  The 
only  reference  to  this  subject  in  recent  German  lit- 
erature is  that  of  Kohnstamm,  (13)  who  relates  a 
number  of  instances  in  which  thyroid,  hypophysis, 
or  adrenal  preparations  were  used  to  improve  the 
morbid  conditions  resulting  from  disturbances  in 
the  internal  secretions  caused  by  the  emotional 
strain  of  the  soldier's  life  while  on  active  service. 

I  believe  that  the  systematic  administration  of 
pluriglandular  extracts  opens  up  a  new  era  in  or- 
ganotherapy. As  an  adjunct  to  other  indicated 
treatment  it  favors  the  restoration  of  the  disturbed 
"hormone  balance,"  so  well  discussed  by  Harry 
Campbell,  (14)  and  others.  The  theoretical  side  of 
this  subject  is  outlined  quite  fully  in  my  book,  (15) 
and  since  its  publication  I  have  had  many  oppor- 
tunities to  test  its  efricacy  in  civil  practice.     I  be- 


74  THE  INTERNAL  SECRETIONS 

lieve  that  it  will  be  just  as  efficacious  in  the  treat- 
ment of  soldiers,  and  that  the  results  already  se- 
cured are  a  pleasant  foretaste  of  what  may  be  ex- 
pected by  applying  this  suggestion  much  more  ex- 
tensively. 


Since  the  above  was  published  it  has  come  to  my 
attention  that  the  application  of  pluriglandular 
therapy  in  similar  conditions  both  in  this  country 
and  abroad  is  indeed  an  efficacious  measure,  even 
though  the  foregoing  explanation  may  not  be  be- 
yond discussion.  One  case  in  particular  comes  to 
mind:  A  man,  previously  in  good  health,  went 
through  a  "near  accident"  but  was  not  hurt.  His 
blood  pressure  was  80  mm.,  his  temperature  was 
subnormal,  his  heart  action  hurried  and  he  was  ob- 
viously suffering  from  shock.  Tonic  organother- 
apy "acted  like  a  charm"  and  by  the  thermometer, 
sphygmomanometer  and  stethoscope  it  seemed 
quite  clear  that  a  very  tangible  service  had  been 
rendered. 

Another  case  of  a  somewhat  similar  nature  was 
recently  reported  by  Dr.  Vanderwyst  of  Kansas.  A 
girl  of  17  had  manifested  a  neurosis  for  five  years 
following  a  severe  experience  with  a  cyclone  when 
she  was  twelve  years  old.  Since  then  her  tempera- 
ture has  been  very  unstable,  she  suffered  from  vari- 
ous vasomotor  disturbances  and  was  subject  to  se- 
vere emotional  "storms."  She  was  much  run  down, 
anemic  and  suffered  from  transitory  attacks  of  pain 


IN  PRACTICAL  MEDICINE  75 

in  different  parts  of    the    body,  especially  in  the 
spine. 

After  varied  and  protracted  treatment  she  was 
given  a  course  of  pluriglandular  therapy  repre- 
sented by  the  Roberts-Hawley  Lymph  with  a  very 
remarkable  re-establishment  of  normal  emotional 
and  nervous  stability  as  well  as  an  accompanying 
gain  in  weight  and  health. 

This  is  but  an  additional  indication,  to  the  writer 
at  least,  that  the  dynamic  or  antiasthenic  effect  of 
hormone  therapy  is  deserving  of  consideration  in 
the  neurasthenic  manifestations  due  to  or  akin  to 
"shell  shock." 

REFERENCES 

1.  Elliott:  Jour.  Physiol,  1905,  xxix,  363;   1912,  xliv, 
374. 

2.  Cannon,  et  al. :  Amer.  Jour.  Physiol.,   1911,  xxviii, 
64;  1911,  xxix,  274;  1914,  xxxiii,  356. 

3.  Editorial:    Amer.  Med.,  1915,  xxi,  590. 

4.  Crile :     Surg.  Gyn.  and  Obs,  1915,  xvii,  708. 

5.  Smith :    Lancet,  1916,  cxc,  813. 

6.  Renon :    Jour,  des  Practiciens,  Jan.  15,  1915. 

7.  Editorial :    Jour.  Amer.  Med.  Assoc,  1915,  lxv,  2166. 

8.  Williams  :  Jour.  Amer.  Med.  Assoc.,  1914,  lxiii,  2203. 

9.  Corbett :    Jour.  Amer.  Med.  Assoc,  1915,  lxv,  380. 

10.  Mackenzie:  British  Med.  Jour.,  1916,  i,  117. 

11.  Sergent:     Bull.  Acad.  Med.  Paris,  Sept.  7,  1915; 
see  Amer.  Med.,  1915,  xxi,  922. 

12.  Holmes :    Lancet-Clinic,  1914,  cxiii,  705. 

13.  Kohnstamm :     quoted  m   Critic  and  Guide,   1916, 
xix,  153. 

14.  Campbell:    Lancet,  1907,  i,  313  et  seq. 

15.  Harrower:     "Practical  Hormone  Therapy,"  Bal- 
liere,  1914. 


VII 

THE  ADRENAL  GLANDS  AND  THEIR  SIG- 
NIFICANCE IN  GENERAL  PRACTICE 

THE  study  of  the  adrenal  glands  has  received  a 
great  impetus  since  Cannon  recently  announced 
his  epoch-making  discoveries  of  the  physiological 
changes  in  these  glands  dependent  upon  the  emo- 
tions. The  practical  application  of  this  new  knowl- 
edge is  important,  though  it  is  not  yet  appreciated 
as  much  as  it  deserves.  Sometimes  it  takes  a  long 
time  for  the  experiences  of  the  physiologists  in 
their  laboratories  to  be  translated  into  terms  of 
every-day  utility  to  the  practicing  physician;  and 
in  my  somewhat  broad  association  with  physicians 
in  different  parts  of  the  world,  during  which  we 
have  almost  invariably  discussed  matters  pertain 
ing  to  the  internal  secretions,  I  have  noticed  quite 
a  lack  of  appreciation  of  the  clinical  value  of  Can- 
non's work. 

Briefly,  we  now  know  that  the  emotions,  fear, 
rage  and  pain,  stimulate  the  adrenal  glands;  and  it 
is  believed  that  many  of  the  phenomena  which  usu- 
ally accompapny  emotional  strain,  really  result 
from  the  excessive  amount  of  adrenin  liberated 
from  the  adrenal  medulla  by  the  psychic  stimuli;  or 
from  the  glandular  depletion  which  one  would  nat- 


Read  by  invitation  before  the  Pasadena  branch  of  the  Los 
Angeles  County  Medical  Association,  and  published  in  the  Medi 
cal  Review  of  Reviews  (New  York)  May,  1917. 

(76) 


IN  PRACTICAL  MEDICINE  77 

urally  expect  to  follow  excessive  functional  activ- 
ity. 

I  am  confident  that  if  this  fundamental  physio- 
logical principle  were  kept  in  mind,  and  the  connec- 
tion between  the  adrenals  and  certain  affections 
was  understood,  the  appreciation  of  this  usually 
overlooked  element  would  make  a  good  deal  of  dif- 
ference to  the  diagnostics  and  the  therapeutics  of 
these  conditions — would  further  revolutionize  our 
conceptions  of  disease.  It  is  for  these  reasons  that 
I  have  chosen  this  subject  for  brief  consideration 
to-night,  and  I  am  confident  that  much  practical 
good  can  come  from  the  clinical  application  of  Can- 
non's remarkable  experiments.  To  those  who  may 
become  interested  in  the  intricacies  of  this  matter 
J  warmly  recommend  Cannon's  book,  "Bodily 
Changes  in  Pain,  Hunger,  Fear  and  Rage,"*  in 
which  the  subject  is  considered  from  its  experi- 
mental aspect.    It  is  a  fascinating  book. 

With  these  new  principles  in  mind  we  can  now 
begin  to  explain  the  sudden  onset  of  serious  symp- 
toms and  even  diseases,  following  some  severe 
mental  shock.  We  can  understand  more  thor- 
oughly the  comparatively  recently  discussed  kinetic 
system,  as  well  as  what  Crile  pleases  to  call  "anoci- 
association,"  both  of  which  are  intimately  related 
with  the  function  of  the  adrenal  glands,  especially 
as  it  is  influenced  by  pain,  mental  stimuli  and  the 


*D.  Appleton  &  Company,  New  York,  1915.     $2.00. 


78  THE  INTERNAL  SECRETIONS 

emotions.  There  is  a  much  wider  application  of 
this  than  that  which  is  being  so  successfully  applied 
by  Crile  and  his  followers  in  their  surgical  work. 

Let  us  first  recall  the  physiological  reactions 
which  result  from  excessive  or  deficient  adrenemia. 
An  increased  output  of  the  chromaffin  hormone, 
adrenin,  favors  the  production  of  an  increased  sym- 
pathetico-tonus,  increases  the  reactivity  of  the  or- 
ganism to  all  sorts  of  impressions,  augments  car- 
diac action,  raises  the  arterial  tension,  hinders  in- 
testinal motility  and  causes  a  decrease  in  the  func- 
tions of  the  pancreas,  especially  as  regards  its  in- 
ternal secretory  capacity  with  possible  glycosuria 
(clinically  analogous  to  the  experimental  "adren- 
alin glycosuria"  following  injections  of  this  sub- 
stance, as  well  as  to  the  "experimental  pancreatic 
diabetes"  which  invariably  follows  removal  of  the 
islets  of  Langerhans). 

On  the  other  hand  the  chromaffin  cells  may  be 
so  unduly  stimulated  that  they  become  transiently, 
or  even  permanently,  played  out;  and  a  condition  of 
adrenal  insufficiency  ensues,  which  is  quite  com- 
mon in  general  practice  as  we  will  shortly  see.  This 
hypoadrenia  is  responsible  for  reduced  sympathetic 
tone,  lessened  muscular  excitability  and  capacity 
with  exhaustion  on  slight  exertion,  or  asthenia 
(quite  the  most  prominent  and  constant  symptom 
of  this  disturbance),  reduced  cardiac  power  and, 
sometimes,  rate,  lessened  blood  pressure  and, 
finally,  collapse  or  shock  with  pallor,  clammy,  cold 


IN  PRACTICAL  MEDICINE  79 

skin,  dilated  pupils  and  respiratory  excitement  and, 
later,  failure. 

To  my  mind  it  is  quite  proper  to  consider  a  pos- 
sible adrenal  cause  for  each  symptom  just  enumer- 
ated. Very  often  it  may  be  the  chief  cause  and, 
too,  other  causes  which  also  may  be  present  are  in 
part  due  to  the  adrenal  factor. 

Perhaps  we  might  recapitulate  just  what  Cannon 
demonstrated.  He  showed  that  the  emotion  of  fear 
suffices  to  cause  an  increased  stimulation  of  the 
flow  of  the  adrenal  secretion,  and  blood  taken  from 
the  adrenal  veins  of  frightened  animals  is  so  rich 
in  adrenin  as  to  be  able  to  inhibit  the  peristaltic 
contraction  of  isolated  strips  of  intestinal  muscle 
which  were  immersed  in  the  blood.  This  also  has 
been  shown  to  result  from  the  presence,  in  appre- 
ciable amount,  of  adrenalin  since  contact  with  this 
commercial  chemical  substance  in  a  dilution  as  in- 
significant as  1 :1,000,000  will  bring  about  the  same 
experimental  results  upon  isolated  intestine. 

Some  day  a  comparatively  easy  technic  will  be 
evolved  for  the  clinical  measurement  of  adrenal 
activity.  Many  a  time  I  have  wished  that  I  might 
be  able  to  determine  the  degree  of  adrenal  function- 
ing in  a  given  case.  For  example,  some  individuals 
are  more  susceptible  to  external  impressions  than 
others,  and  of  these  there-  are  some  who  suffer 
much  longer  as  a  result  of  serious  excitement  than 
others;  they  "take  a  long  time  to  get  over"  such 
experiences.     If,  now,  we    were    able    to    estimate 


80  THE  INTERNAL  SECRETIONS 

with  some  degree  of  comparison  the  adrenin  con- 
tent of  the  blood  of  these  persons,  we  would  be  able 
to  know  whether  the  adrenal  element  was  promi- 
nent, could  measure  the  degree  of  its  depletion  or 
excitation,  and,  naturally,  would  be  better  able  to 
control  the  deviations  from  the  average. 

On  the  other  hand,  in  cases  suffering  from  the 
after  effects  of  this  excessive  stimulation,  as  in 
shock,  collapse  or  severe  asthenia,  we  might  be  able 
to  estimate  in  actual  figures  the  factor  of  restora- 
tion and  see  how  well  and  how  rapidly  the  depleted 
adrenals  were  unable  to  functionate.  In  other 
words,  we  would  be  able  to  measure  hyper-  or  hypo- 
adrenia. 

A  means  of  accomplishing  this  has  been  sug- 
gested by  Ehrmann,  and  is  sometimes  called  "the 
frog's  eye  test/'  It  consists  of  immersing  a  re- 
cently enucleated  frog's  eye  into  the  blood  serum 
of  the  patient  under  examination.  One  notes  the 
time  elapsing  from  the  moment  that  the  eye  is  im- 
mersed in  the  serum,  until  the  pupil  reaches  maxi- 
mum dilatation.  This  may  be  compared  with  a 
scale  previously  made  by  performing  the  same  ex- 
periment with  definite  solutions  of  adrenalin.  It  is 
thus  possible  to  estimate  comparatively  the  amount 
of  adrenin  present  in  the  blood  serum  examined, 
though  this  method  is  somewhat  crude  and  by  no 
means  accurate,  for  we  do  not  know  with  certainty 
that  the  mydriasis  is  of  purely  hormonic  origin. 
Also  adrenin  and  adrenalin  are  very  easily  oxidiz- 


IN  PRACTICAL  MEDICINE  81 

able  substances,  and  this  militates  against  an  alto- 
gether dependable  test.  There  is  no  doubt,  how- 
ever, that  some  day  we  will  have  a  clinical  diag- 
nostic procedure  for  the  determination  of  the  ex- 
tent of  the  adrenal  activities.  I  have  suggested 
that  some  sort  of  a  colorimetric  test  should  be  pos- 
sible, and  before  long  I  believe  that  some  chemist 
or  physician  is  going  to  work  it  out. 

The  interrelation  of  the  endocrine  glands  is  so 
complex  and  intimate  that  it  is  practically  impos- 
sible to  have  a  marked  deviation  from  the  func- 
tional normal  of  one  gland  without  a  correspond- 
ing increase  or  decrease  in  the  work  of  the  others. 
This  is  the  basis  of  the  complexities  of  endocrinol- 
ogy and  the  reason  for  the  numerous  reports  of 
pluriglandular  disorder  we  are  beginning  to  find  in 
the  literature.  Parenthetically,  it  is  often  also  the 
reason  for  failures  in  the  treatment  of  this  class  of 
cases,  for  a  presumed  thyroid  disorder  is  treated  as 
a  thyroid  disorder  pure  and  simple,  when  further 
investigation  would  couple  one  or  more  glands 
with  it — often  the  pituitary,  gonads  or  adrenals — 
and  the  treatment  modified  by  this  broader  view 
would  be  much  more  effectual. 

So  adrenal  stimulation  by  emotional  causes,  bv 
toxemia  or  by  changes  in  the  hormone  balance, 
may  cause  other  ductless  glandular  disorders.  For 
instance,  fright  often  has  much  to  do  with  the 
onset  of  hyperthyroidism.  I  have  seen  a  severe 
shock  cause  exophthalmic  goiter  over  night.  Crotti 


82  THE  INTERNAL  SECRETIONS 

mentions  the  case  of  a  man  of  42  who  had  Graves' 
disease  which  developed  in  a  few  hours  at  the  time 
of  the  San  Francisco  earthquake.  I  commonly  find 
indications  of  this  relationship  in  my  consultation 
work,  and  there  are  numerous  reports  in  the  litera- 
ture to  substantiate  this.  In  such  cases  I  am  con- 
vinced that  the  etiologic  influence  is  not  so  much 
nervous  as  hormonic;  and  I  explain  this  to  myself 
by  presuming  that  the  undue  stimulation  of  the  ad- 
renals by  emotional  strain  causes  a  severe  increase 
in  their  secretory  activities  which,  so  to  speak, 
gives  a  very  strong  push  to  the  thyroid  pendulum, 
causing  it  to  swing  much  more  rapidly  and  in  a 
longer  arc. 

While  we  are  speaking  of  hyperthyroidism,  T 
would  like  to  remark  that  anger,  fear  and,  espe- 
cially, worry  are  factors  which  play  a  very  im- 
portant part  in  the  treatment  of  all  forms  of  this 
disorder.  I  have  a  case  at  present  in  whom  the 
symptoms  are  always  aggravated  by  concern  over 
home  matters,  and  the  best  of  treatment,  with  ab- 
solute rest  in  hospital  or  out,  is  largely  overbal- 
anced by  the  fears  and  worries  so  difficult  to  con- 
trol. A  part  of  the  proper  treatment  of  hyperthy- 
roidism is  not  merely  rest,  but  absolute  quiet  away 
from  the  "hospital  noises"  and  the  removal  of  all 
things  likely  to  disturb  the  emotional  balance;  in 
other  words  the  prevention  of  adrenal  stimulation 
just  as  Crile  prevents  this  same  thing  in  his  surgi- 
cal work  by  his  methods  of  pan-anesthesia.     The 


IN  PRACTICAL  MEDICINE  83 

administration  of  adrenalin,  or  the  equally  useful 
adrenal  substance,  may  in  some  cases  offset  severe 
adrenal  depletion. 

Undoubtedly  adrenal  dysfunction  is  capable  of 
causing  digestive  disorders.  Crile  has  shown  ex- 
perimentally that  among  the  functions  of  the  ad- 
renals is  the  power  to  inhibit  intestinal  function 
provided  the  adrenals  are  working  to  excess.  Can- 
non confirms  this,  and  has  proved  that  a  forced  out- 
put of  adrenin  produces  an  increase  in  the  arterial 
tension  by  shifting  the  blood  from  the  compara- 
tively less  important  abdominal  viscera  to  the  im- 
mediately essential  organs  as  the  brain,  lungs  and 
heart.  It  seems  that  there  is  enough  clinical  proof 
to  implicate  the  adrenals  in  epilepsy.  Adrenal  ex- 
cess tends  to  increase  circulatory  stasis  in  the  brain, 
inhibits  both  pancreatic  digestion  and  intestinal 
muscular  activity  and  thus  favors  toxemia;  factors 
which  unquestionably  are  prominent  in  the  syn- 
drome of  epilepsy.  We  all  know  that  fright  may 
be  a  part  of  the  original  cause  of  epilepsy,  and  also 
that  a  sudden  shock  or  grief  may  badly  upset  the 
digestion. 

Some  interesting  comments  on  the  relation  of 
the  adrenals  to  intestinal  stasis  and  epilepsy  are  to 
be  found  in  a  recent  paper  coming  from  the  New 
Jersey  State  Hospital.  Cotton  and  his  associates 
there  conclude  that  at  least  one  type  of  epilepsy  is 
probably  a  disease  process  dependent  upon  the  ab- 
sorption of  toxic  products  from  the  intestinal  canal. 


84  THE  INTERNAL  SECRETIONS 

This  stasis  may  be  produced  by  an  overaction  of 
the  adrenal  glands  which,  in  turn,  may  be  caused 
by  dysfunction  of  the  pituitary  body  or  the  pan- 
creas, irritation  of  the  duodenum,  or  severe  fright 
or  emotional  disturbance.  They  then  suggest  that 
the  administration  of  pancreatin  should  be  em- 
ployed in  preference  to  surgical  measures  in  the 
treatment  of  epilepsy.  Incidentally  this  form  of 
organotherapy  is  physiologically  opposed  to  the 
action  of  the  adrenals;  it  favors  digestion,  and  it 
has  been  remarked  that  the  pituitary  is  also  an 
antagonist  of  the  pancreas.  At  least  Cotton's  25 
or  30  cases  encouraged  him  to  make  the  above  de- 
ductions and  to  report  his  good  results  with  pan- 
creatic organotherapy  in  epilepsy.  I  mention  this 
for  what  it  is  worth ;  at  least  it  amplifies  my  opinion 
regarding  the  importance  of  the  adrenals  in  this 
disease.  Note  especially  that  toxemia  causes  hyper- 
adrenia;  that  hyperadrenia  causes  toxemia  (a  vi- 
cious circle)  and  intestinal  insufficiency,  factors  in- 
volved in  many  another  syndrome  besides  epilepsy. 
Pottenger  has  been  doing  some  very  interesting 
work  involving  the  adrenal  glands  with  some  of  the 
findings  in  certain  forms  of  pulmonary  tubercu- 
losis. He  has  shown  quite  recently  that  the  con- 
tinued stimulation  of  the  adrenals,  presumably  by 
the  toxins  of  this  disease,  and  the  continued  pour- 
ing into  the  blood  of  even  minutely  increased 
amounts  of  adrenin,  brings  about  conditions  re- 
sulting   from    sympathetic    stimulation,  including 


IN  PRACTICAL  MEDICINE  85 

the  very  dry  mouth  not  uncommonly  seen  in  tuber- 
culosis, as  well  as  other  clinical  findings,  as  the 
rapid  heart  action  and  the  sudden  and  quite  serious 
disturbances  of  digestion  that  one  meets  from  time 
to  time  in  tuberculosis. 

I  have  put  forward  a  theory  regarding  the  ad- 
renals in  malaria  which  is  yet  to  be  discredited  or 
proved.  I  believe  that  at  one  stage  in  the  cycle  of 
experiences  in  malaria  there  is  a  decided  adrenal 
excitation,  due  to  the  sudden  periodical  liberation 
of  the  plasmodia  and,  of  course,  their  toxins.  One 
encounters  the  dry  mouth  as  often  as  salivation, 
both  manifestations  of  sympathetic  stimulation. 
The  heart  action  is  always  rapid  and  sometimes  ir- 
regular. Then,  as  an  aftermath  of  the  chill,  we  find 
the  muscular  relaxation,  prostration,  depression 
and  asthenia,  all  of  which  are  identical  with  the 
findings  of  severe  adrenal  insufficiency. 

If  this  idea  is  reasonable  it  should  apply  with 
equal  force  in  other  toxic  infectious  diseases  and 
acute  toxemias,  such  as  typhoid  fever  and  pneu- 
monia; and  Josue,  Sergent  and  other  French  writ- 
ers have  accumulated  undeniable  evidence  to  show 
that  the  ultimate  outcome  of  acute  infectious  dis- 
ease includes  a  very  severe  adrenal  depletion  which 
not  uncommonly  may  be  the  actual  cause  of  death. 

The  most  frequent  form  of  serious  adrenal  dis- 
order, then,  is  not  Addison's  disease,  but  what 
Sajous  has  called  "terminal  hypoadrenia."  This  is 
the  frequently  fatal  ending  of  septicemia  and  all 


86  THE  INTERNAL  SECRETIONS 

serious  toxemias  as  diphtheria,  cholera  and  the  like. 
In  fact  the  algid  stage  of  cholera,  like  the  fatal 
"turn  for  the  worse"  in  erysipelas  or  pneumonia,  is 
brought  on  when  the  severe  bacterial  poisoning 
and  accompanying  cellular  depletion  causes  acute 
hypoadrenia  with  collapse,  heart  weakness,  a  drop 
in  the  temperature  and  death.  In  such  desperate 
stages  the  tide  has  been  turned  by  intravenous  in- 
jections of  adrenalin,  as  much  as  30  min.  of  the 
1 :1000  solution  having  been  given  with  a  happy 
outcome.  This  fundamental  principle  is  worth  re- 
membering in  such  extremes,  for  the  logical  treat- 
ment is  occasionally  amazingly  resurrective. 

In  gynecological  practice  the  adrenal  glands  may 
play  an  important  role.  I  shall  shortly  direct  your 
attention  to  their  relationship  to  neurasthenia,  and 
here  wish  you  to  recall  the  frequency  with  which 
severe  asthenia  accompanies  ovarian  disease.  To 
illustrate,  I  recentlv  saw  a  case  in  Omaha  of  ex- 
treme  asthenia.  This  came  on  pepriodically  in  con- 
nection with  the  menses,  and  during  the  month 
there  were,  perhaps,  five  or  six  days  in  which  the 
extreme  lassitude  and  inability  to  accomplish  any- 
thing were  slightly  modified.  The  weakness  was 
absolute  and  had  continued  for  years.  The  diag- 
nosis was  hypoadrenia  superinduced  by  dysovarian 
or  ovarian  toxemia.  In  this  case  surgery  gave 
some  benefit,  I  believe,  for  a  diseased  ovary  was 
removed  in  my  presence  and  a  cyst  in  the  other 
was  also  removed.     From  the  standpoint  of  this 


IN  PRACTICAL  MEDICINE  87 

paper  the  case  was  of  special  interest,  for  the  myas- 
thenia as  well  as  the  neurasthenia  was  undoubtedly 
due  to  the  abnormal  stimulation  of  the  chromaffin 
cells  by  this  poisonous  ovarian  hormone,  and  the 
patient  was  thus  in  a  practically  perpetual  state  of 
hypoadrenia. 

I  do  not  wish  to  commit  myself  to-night,  but  I 
have  studied  a  number  of  cases  of  functional  dys- 
menorrhea from  the  standpoint  of  endocrinology, 
and  I  must  confess  that  I  have  strong  suspicions 
that  many  of  the  symptoms,  especially  those  of  a 
sympathetic  nature,  are  of  adrenal  origin;  and  if 
so  the  trouble  is  probably  brought  about  by  this  re- 
flex (hormonic)  stimulation  of  the  adrenals  by  the 
ovaries. 

There  is  much  reason  to  believe  that  adrenal  dys- 
function is  a  factor  which  deserves  a  good  deal 
more  responsibility  placed  upon  it  for  the  causation 
of  neurasthenia  than  as  yet  has  been  given  to  it. 
In  a  recent  article  in  my  series,  "The  Diagnosis  of 
the  Internal  Secretory  Disorders"  (Western  Medi- 
cal Times,  Sept.,  1916)  you  will  find  an  outline  of 
some  facts  connecting  the  adrenals  with  neuras- 
thenia.    I  will  quote  a  few  paragraphs  here: 

"Minor  functional  hypoadrenia  is  more  common 
than  some  have  appreciated,  and  the  fact  that  there 
is  a  psychic  origin  as  well  as  other  physiologic 
causes  already  considered,  allies  it  to  the  fashion- 
able 'neurasthenia'  of  to-day.  In  fact  some  have 
stated  that  what  is  improperly  called  'neurasthenia' 


88  THE  INTERNAL  SECRETIONS 

is  not  a  disease  per  se,  but  really  a  symptom  com- 
plex of  ductless  glandular  origin,  and  that  the  ad- 
renals are  probably  the  most  important  factors  in 
its  causation.  Campbell  Smith,  O.  T.  Osborne, 
Tom  Williams  and  others,  including  the  writer, 
have  directed  the  attention  of  the  profession  to  the 
importance  of  the  adrenal  origin  of  neurasthenia 
(though  a  pluriglandular  dyscrasia  is  practically 
always  discoverable),  but  so  far  this  is  not  under- 
stood as  well  as  its  frequency  and  importance  war 
rant. 

"The  subject  is  too  large  to  receive  exhaustive 
consideration  here,  but  a  few  quotations  from  re- 
cent literature  will  firmly  establish  the  importance 
of  this  angle  from  which  to  study  this  common  and 
annoying  symptom  complex.  Quoting  first  from 
the  Journal  of  the  American  Medical  Association 
(Dec.  18,  1915,  p.  2166)  :  'The  typical  neurotic  gen- 
erally has,  if  not  always,  disturbance  of  the  thyroid 
gland.  The  typical  neurasthenic  probably  gener- 
ally has  disturbance  of  the  suprarenal  glands  on 
the  side  of  insufficiency.  The  blood  pressure  in 
these  neurasthenic  patients  is  almost  always  low 
for  the  individuals,  and  their  circulation  is  poor.  A 
vasomotor  paralysis,  often  present,  allows  chill- 
ings,  flushings,  cold  or  burning  hands  and  feet, 
drowsiness  when  the  patient  is  up,  wakefulness  on 
lying  down  and  hence  insomnia.  There  may  be 
more  or  less  tingling  or  numbness  of  the  extremi- 
ties/ 


IN  PRACTICAL  MEDICINE  89 

"Again  Kinnie  Wilson,  of  London,  in  his  mono- 
graph on  'The  Clinical  Importance  of  the  Sympa- 
thetic Nervous  System'  makes  the  following  perti- 
nent remarks:  'Many  of  the  common  symptoms 
of  neurasthenia  and  hysteria  are  patently  of  sympa- 
thetic origin.  Who  of  us  has  not  seen  the  typical 
irregular  blotches  appear  on  the  skin  of  the  neck 
and  face  as  the  neurasthenic  subject  "works  him- 
self up  into  a  state"?  The  clammy  hand,  flushed 
or  pallid  features,  dilated  pupils,  the  innumerable 
paresthesias,  the  unwonted  sensations  in  head  or 
body,  are  surely  of  sympathetic  parentage.  In  not 
a  few  cases  of  neurasthenia  symptoms  of  this  class 
are  the  chief  or  only  manifestations  of  the  disease. 
Here,  then,  is  a  condition  of  defective  sympathet- 
ico-tonus;  may  it  not  have  much  to  do  with  im- 
pairment of  function  of  the  chromophil  system? 
.  .  .  There  does  not  appear  to  be  any  tenable  dis- 
tinction between  the  asthenia  of  Addison's  disease 
and  the  asthenia  of  neurasthenia.  Cases  of  the  for- 
mer are  not  infrequently  diagnosed  as  ordinary 
neurasthenia  at  first.  It  is  difficult  to  avoid  the  con- 
clusion that  defect  of  glandular  function  is  respons- 
ible for  much  of  the  clinical  picture  of  neuras- 
thenia.' " 

Be  prepared  to  look  for  the  adrenal  element  in 
gynecology  or  in  neurasthenia  and  it  will  surprise 
you  how  common  it  really  is.  Kinnie  Wilson,  in 
the  same  address  from  which  the  above  quotation 
was    made,   also    made    the    following   apothegm: 


90  THE  INTERNAL  SECRETIONS 

"Sympathetic  tone  is  dependent  on  adrenal  sup- 
port, and  until  the  glandular  equilibrium  is  once 
more  attained,  sympathetic  symptoms  are  likely  to 
occur." 

In  closing  I  might  point  out  that  these  reactions 
resulting  from  adrenal  excess  possibly  may  explain 
the  occasional  effects  of  psychanalysis,  suggestion 
and  even  Christian  Science  in  certain  neurotic  or, 
more  properly,  sympathetico-tonic  states.  One  can 
readily  see  that  a  calmed  mind — reduced  emotional 
overstrain — obviates  the  excessive  psychic  stimula- 
tion of  the  adrenals;  and  the  hypertonic  state  of 
hyperadrenia  or  the  later  asthenic  state  of  hypo- 
adrenia  are  thereby  allowed  to  right  themselves  by 
Nature. 

This  may  be  visionary,  but  I  still  insist  that  we 
are  going  to  connect  the  adrenal  glands  with  nu- 
merous conditions  encountered  in  general  practice, 
particularly  those  connected  with  the  emotions, 
more  and  more  as  we  come  to  understand  their 
functions  and  interrelations  better. 


VIII 

THE  ASTHENIAS: 
NEURASTHENIA,    PSYCHASTHENIA,    MY- 
ASTHENIA  AND    CHEMASTHENIA— 
ENDOCRINASTHENIA 

OF  ALL  the  difficulties  encountered  in  general 
practice  the  asthenias  constitute  quite  a  large  per- 
centage. Naturally  neurasthenia  occupies  a  promi- 
nent place,  but  this  is  by  no  means  the  only  asthe- 
nia which  we  have  to  meet.  It  is  the  opinion  of  the 
writer  that  endocrinasthenia  is  a  very  much  more 
important  condition  than  yet  appears.  In  fact  this 
word  is  not  yet  found  in  our  most  recent  diction- 
aries and  while  there  is  plenty  of  literature  upon 
ductless  glandular  insufficiencies,  so  far  as  I  know 
the  subject  has  not  been  extensively  considered 
from  this  angle. 

The  hormones,  or  the  "regulators  of  metabo- 
lism" as  Noel  Paton  has  called  them,  bring  about 
a  series  of  chemical  reactions  which  really  must  be 
considered  as  sthenic  in  character.  The  word  "hor- 
mone" comes  from  the  Greek,  "I  arouse,"  and  it  is 
not  a  very  great  stretch  of  imagination  to  consider 
asthenia  as  representing  "I  lie  down." 

There  is  an  accumulating  weight  of  evidence  in 
clinical  practice  which  is  being  reflected  in  current 
literature  which  indicates  that  many  forms  of  as- 
thenia properly  may  be  called  of  endocrine  origin 

(91) 


92  THE  INTERNAL  SECRETIONS 

or  endocrinasthenia.  The  arousing  stimuli  are  les- 
sened or  lost.  The  body,  or  a  part  of  it  as  the  case 
may  be,  is  tired  out,  function  has  been  disorganized 
by  numerous  factors  and  the  resulting  loss  of 
strength  and  activity  may  affect  the  muscles, 
nerves,  mentality,  metabolism  or,  for  that  matter, 
any  other  bodily  function.  It  seems  quite  reason- 
able to  believe  that  if  the  endocrine  glands  are  af- 
fected by  conditions  which  render  them  inactive, 
the  natural  outcome  would  be  a  condition  of  gen- 
eral functional  somnolence,  or  as  we  call  it  "asthe- 
nia"; while  any  attempt  to  bring  about  greater 
activity  on  the  part  of  the  glands  of  internal  secre- 
tion must  necessarily  arouse  the  metabolic  func- 
tions in  general  as  well  as  certain  of  the  results  of 
this  hormonic  function  in  particular. 

If  this  is  the  case,  we  must  revise  our  consid- 
eration of  the  origin  as  well  as  the  treatment  of  all 
forms  of  asthenia  and  from  a  practical  standpoint 
this  seems  to  be  a  profitable  advance  in  medicine, 
for  when  we  treat  the  various  asthenias  with  the 
internal  secretory  factor  prominently  in  our  minds, 
the  results  really  seem  to  be  better  and  more  per- 
manent than  though  we  merely  prescribe  rest  and 
a  hygienic  regimen  calculated  to  reduce  the  tox- 
emia. 

Of  course  rest  is  most  advantageous  in  the  treat- 
ment of  all  forms  of  fatigue  whether  natural  or 
pathologic,  though  many  individuals  suffer  from 
forms  of  tiredness  which  are  not  remedied  by  in- 


IN  PRACTICAL  MEDICINE  93 

activity  and  sleep — they  are  the  ones  who  "get  up 
tired."  Preventive  measures  usually  do  not  suffice 
to  secure  tangible  results  in  cases  of  this  charac- 
ter, and  treatment  calculated  to  remove  as  many  of 
the  obvious  conditions  favoring  the  asthenia  is  very 
much  more  satisfactory  in  its  results  if  efforts  are 
made  simultaneously  to  re-establish  the  normal  hor- 
mone producing  functions. 

With  these  preliminary  considerations  in  mind 
we  will  consider  briefly  the  various  asthenic  states 
and  attempt  to  connect  them  with  one  or  more  of 
the  glands  of  internal  secretion  and,  having  done 
so,  it  must  be  left  to  the  reader  to  apply  his  own 
deductions  and  modify  his  treatment  of  asthenic 
states  accordingly. 

To  those  who  take  time  to  study  endocrinology 
in  its  relation  to  the  practical  side  of  medicine,  it 
becomes  quickly  apparent  that  the  most  important 
functions  of  the  glands  of  internal  secretion  are  of 
an  aggressive  or  stimulating  nature,  and  further, 
that  the  most  common  endocrine  disorders  are  in 
the  nature  of  an  insufficiency.  With  all  such  insuffi- 
ciencies, whether  they  be  thyroid,  pituitary,  adrenal 
or  gonad  in  origin,  asthenia  is  an  almost  invariable 
accompaniment.  The  chief  diagnostic  or  clinical 
necessity  then,  would  appear  to  be  the  appreciation 
of  early  forms  of  endocrine  insufficiency  or  hypo- 
crinism  and,  where  possible,  the  differentiation  or 
evaluation  of  functional  insufficiency  of  the  glands 
that  are  affected. 


94  THE  INTERNAL  SECRETIONS 

The  thyroid  gland  is  responsible  for  a  very  large 
measure  of  the  metabolic  activities  of  the  body  and 
is  susceptible  to  the  subtle  influences  of  numerous 
very  common  disorders,  for  toxemia  of  all  kinds 
affects  the  thyroid  as  early  as  any  other  part  of 
the  body  and  infections,  whether  general  or  focal, 
not  infrequently  disturb  the  normal  functioning  of 
this  gland.  The  French  have  called  the  thyroid 
"the  emotional  srland"  since  it  is  intimatelv  related 
to  the  emotions,  but  we  now  believe  that  much  of 
this  supposed  connection  is  not  direct,  but  is 
brought  about  through  the  intimacy  of  the  adrenals 
with  the  thyroid.  Theoretically  these  conditions 
should  stimulate  the  thyroid  and  it  is  perfectly  true 
that  many  cases  of  thyroid  excess  are  the  result 
of  just  such  stimuli,  but  it  is  none  the  less  a  clinical 
fact  that  insufficiencies  are  more  frequent  than  the 
opposite  conditions  and  hypothyroidism,  especially 
the  minor  form,  is  very  much  more  common  than 
hyperthyroidism. 

The  clinical  importance  of  the  minor  forms  of 
thyroid  insufficiency  has  been  fully  discussed  else- 
where* and  if  the  study  of  individuals  suffering 
from  any  form  of  asthenia  is  made  to  include  a 
search  for  definite  indications  which  would  lead 
one  to  incriminate  the  thyroid  gland,  treatment  cal- 
culated to  stimulate  this  gland  is  very  likely  to 
make  a  favorable  impression  upon  the  course  of  the 


*See  Chapter  IV. 


IN  PRACTICAL  MEDICINE  95 

disorder,  f  If  one  reads  much  of  the  literature  on 
thyroid  disorders  and  even  limits  it  to  the  writings 
of  Eugene  Hertoghe,  Leopold  Levi,  George  Mur- 
ray or  Gabriel  Gauthier  he  will  be  quickly  con- 
vinced of  the  extreme  frequency  of  asthenia  as  a 
manifestation  of  all  forms  of  subthyroidism  from 
the  most  insignificant  and  easily  overlooked  to  the 
best  clinically  defined  or  text-book  varieties. 

Our  knowledge  of  the  adrenal  glands  is  inex- 
tricably connected  with  asthenia  for  the  most 
prominent  of  all  the  symptoms  described  in  1855 
by  Addison,  is  asthenia  of  a  most  marked  type.  Of 
course  Addison's  disease  is  an  organic  adrenal  dis- 
order and  it  is  not  necessary  for  an  individual  to  be 
suffering  from  this  incurable  disorder  in  order  to 
have  the  symptoms  of  functional  adrenal  insuffi- 
ciency. As  a  matter  of  fact  this  latter  disorder  is 
almost  as  common  as  the  minor  functional  thyroid 
troubles  to  which  attention  has  just  been  drawn, 
and  as  we  now  believe  that  the  adrenals  are  de- 
pleted as  a  result  of  the  stimuli  of  emotion,  tox- 
emia, pain  or  certain  disorders  of  other  glands  of 
internal  secretion,  we  can  readily  see  how  easy  it  is 
to  incriminate  these  glands  in  the  asthenias  as  a 
class.  The  clinical  findings  in  severe  hypoadrenia, 
quite  different  from  the  Addison  syndrome,  always 
include  asthenia  as  a  most  prominent  condition,  for 
what  is  shock  or  collapse  if  it  is  not  an  extreme 


*This  treatment,  by  the  way,  may  be  numbered  among  the 
few  "specifics"  which  we  have  in  medicine. 


96  THE  INTERNAL  SECRETIONS 

manifestation  of  vasomotor  as  well  as  muscular  as- 
thenia? 

The  pituitary  gland,  too,  exerts  what  properly 
might  be  called  a  sthenic  effect.  Its  influence  alone 
is  not  quite  so  marked  as  that  of  the  adrenals  or 
the  thyroid,  but  we  know  that  the  posterior  lobe 
at  least  contains  markedly  stimulating  substances 
and  it  should  not  be  improper  to  presume  that  de- 
ficiencies in  the  production  of  this  and  other  simi- 
lar substances  in  either  lobe  of  the  gland  must  exert 
some  opposite  effect  upon  the  organism.  In  fact 
recent  German  writers  have  definitely  connected 
certain  forms  of  cachexia  with  pituitary  insuffi- 
ciency and  seemingly  have  established  their  con- 
tention by  modifying  these  conditions  with  pitu- 
itary feeding. 

We  also  know  that  pituitary  insufficiency  is 
sometimes  responsible  for  a  syndrome  described  by 
Froehlich  and  Bartels  in  which  metabolic  insuffi- 
ciency (chemasthenia)  is  present  as  well  as  a  defi- 
ciency in  the  production  of  the  so-called  dynamo- 
genie  hormones  with  a  resulting  infantilism  or 
asexuality.  I  recall  a  very  interesting  case  of  asex- 
uality  unaccompanied  by  any  findings  which  would 
warrant  the  diagnosis  of  the  Froehlich  syndrome, 
in  which  a  radiographic  examination  of  the  sella 
turcica  showed  a  very  decided  diminution  in  size 
of  the  pituitary  body.  Additional  evidence  from 
the  opposite  side  is  now  discoverable  in  the  litera- 
ture and  I  have  had  some  favorable  clinical  experi- 


IN  PRACTICAL  MEDICINE  97 

ences  myself  with  the  administration  of  pituitary- 
substance  in  functional  impotence. 

Tom  Williams  of  Washington,  in  a  most  inter- 
esting discussion  of  the  endocrine  neurasthenias 
(Medical  Record,  April  14,  1917),  tells  of  an  ob- 
scure condition  in  a  business  man  which  was  de- 
scribed as  "a  general  feeling  of  discomfort,  some- 
times with  intense  fatigue"  which  was  traced  event- 
ually to  a  disorder  of  the  pituitary  gland. 

Without  a  doubt  the  pituitary  must  be  consid- 
ered as  a  possible  factor  in  the  production  of  many 
of  the  asthenic  manifestations  and  while  the  Ab- 
derhalden  test  as  amplified  and  made  practical  in 
the  Corson-White  laboratory  in  Philadelphia,  is 
often  helpful,  it  is  not  so  difficult  to  secure  a  sellar 
radiograph  in  suspected  cases. 

The  thymus  gland  is  perhaps  the  least  appreci- 
ated and  understood  of  the  glands  of  internal  secre- 
tion. Its  persistence  in  the  adult  is  often  accom- 
panied by  a  severe  asthenia,  especially  myasthenia, 
and  thanks  to  the  work  and  writings  of  G.  H. 
Hoxie  of  Kansas  City,  we  are  beginning  to  under- 
stand more  about  this  clinical  relationship.  It 
should  not  be  amiss  in  the  study  of  a  well  defined 
asthenia  which  resists  treatment,  to  establish  or 
rule  out  by  careful  physical  diagnostic  measures 
and  the  X-ray  the  possible  presence  of  a  persistent 
thymus. 

Still  another  gland  recently  has  been  associated 
with  myasthenia.     Timme   (Archives  of  Internal 


98  THE  INTERNAL  SECRETIONS 

Medicine,  Jan.,  1917)  has  intimated  that  that  in- 
tractable neuro-trophic  disease,  myasthenia  gravis, 
may  be  quite  likely  of  endocrine  origin  and  the 
epiphysis  or  pineal  gland  a  possible  source  of  its 
cause.  This  has  not  been  proven,  but  it  may  be 
that  once  again  an  enigma  heretofore  unsolved  will 
be  made  clear  by  a  broader  knowledge  of  endocrin- 
ology. 

The  sex  glands  are  unquestionably  the  drivers  of 
the  organism.  It  is  not  necessary  to  dilate  upon 
the  relation  of  their  activities  to  muscular,  mental 
or  metabolic  function.  There  is  much  clinical  evi- 
dence to  establish  this  position  and  the  renowned 
experience  of  Brown-Sequard  who  injected  testicle 
juice  into  himself  and  discovered  an  immediate  en- 
hancement of  his  physical  powers  and  endurance 
as  well  as  a  diminution  in  the  asthenia  due  to  his 
age,  was  really  the  beginning  of  scientific  organo- 
therapy, and  times  without  number  since  1889  th^ 
hormonic  importance  of  the  gonads  has  been  estab- 
lished experimentally  and  clinically,  as  well  as 
therapeutically. 

The  natural  corollary  of  the  discovery  of  a  gland- 
ular insufficiency  is  an  attempt  to  re-establish  it, 
and  the  most  satisfactory  and  scientific  manner  to 
accomplish  this  is  by  recourse  to  judicious  organo- 
therapy. It  is  true  that  these  insufficiencies  rarely 
are  seen  singly  and  that  ductless  glandular  dis- 
orders invariably  affect  several  or  all  of  these  or- 
gans, hence  while  this  complicates  our  diagnostics 


IN  PRACTICAL  MEDICINE  99 

and  favors  a  tendency  to  empiricism,  none  the  less 
we  cannot  permit  ourselves  to  ignore  endocrine  de- 
ficiencies just  because  we  may  not  be  able  to  label 
them  accurately  or  to  measure  the  comparative  de- 
ficiencies of  this  gland  or  that.  Without  a  doubt 
the  "unscientific"  administration  of  mixed  glandu- 
lar extracts  whether  proprietary  as  "hormotone" 
or  otherwise  (as,  for  example,  the  "Tabloid  mixed 
glands"  suggested  by  E.  B.  McCready  of  Pitts- 
burgh) has  remedied  materially  many  hundreds  of 
cases,  and  it  is  my  custom  when  attempting  to 
treat  an  asthenia,  whether  neurasthenia,  myasthe- 
nia, psychasthenia  or  chemasthenia,  to  consider  it 
always  as  a  manifestation  of  endocrinasthenia  and 
to  supplement  the  hygienic  and  other  allied  meas- 
ures with  the  indicated  glandular  feeding  or,  in 
suitable  cases,  with  the  hypodermic  administration 
of  the  so-called  Roberts-Hawley  lymph  combina- 
tion of  which,  unfortunately,  there  is  still  too  little 
said  in  current  medical  literature. 


IX 

THE  RELATION   OF  THE   INTERNAL  SE- 
CRETIONS TO  NEURASTHENIA 
IN  WOMEN 

"THE  condition  called  'neurasthenia' — a  symp- 
tom-complex rather  than  a  distinct  disease — is  be- 
ing more  carefully  studied  these  days.  Our  knowl- 
edge, however,  still  seems  to  be  just  as  indefinite 
to-day  as  it  has  always  appeared  to  be,  for  the  opin- 
ions regarding  neurasthenia  have  differed  even 
more  than  the  ideas  of  all  medical  men  usually  dif- 
fer. It  would  appear  that  the  organs  of  internal 
secretion  are  to  be  charged  with  causing  many  of 
the  disorders  which  together  form  the  neurasthenic 
syndrome.  In  fact  the  more  we  study  the  neuras- 
thenic individual  and  observe  closely  the  incidental 
variations  in  functional  activity,  the  more  evident 
it  becomes  that  neurasthenia  rarely  exists  without 
some  associated  disturbance  in  the  work  of  the 
ductless  glands." 

The  foregoing  quotation  from  an  editorial  in 
American  Medicine  (August,  1915,  p.  590)  is  a  fit 
introduction  to  the  subject  that  has  been  chosen 
for  consideration  this  evening.  As  our  knowledge 
of  these  glands  of  internal  secretion  becomes  more 
extensive  and  connected,  one  can  appreciate  more 


An  address  read  before  the  Los  Angeles  Obstetrical  Society, 
December  14,  1915,  and  reprinted  from  the  American  Journal  of 
Obstetrics  and  Diseases  of  Women  and  Children,  April,  1916. 

(100) 


IN  PRACTICAL  MEDICINE  101 

thoroughly  how  intimate  is  their  association  with 
one  another,  as  well  as  with  the  etiology  of  many 
functional  disorders  and  even,  occasionally,  an  or- 
ganic disease.  In  no  phase  of  endocrinology  do  we 
see  that  intricacy  of  these  relationships  more  defi- 
nitely, than  in  the  numerous  functional  disorders, 
the  treatment  of  which  constitutes  the  largest  part 
of  the  work  of  the  gynecologist. 

From  the  time  that  the  thymus  begins  to  retro- 
grade and  its  antagonism  to  the  functional  activity 
of  the  gonads  is  gradually  reduced,  there  is  an  in- 
crease in  the  physiologic  activities  of  the  thyroid 
and  the  ovaries,  as  well  as  in  most  of  the  other 
ductless  glands  which  are  built  in  with  these  key- 
stones of  the  endocrine  arch.  It  is  an  everyday  oc- 
currence to  see  thyroid  enlargement  at  puberty, 
and  it  is  now  well  known  that  the  essential  sex 
manifestations  as  well  as  the  organic  changes 
which  accompany  them,  are  due  to  the  production 
of  a  series  of  chemical  messengers  and  the  main- 
tenance between  them  in  the  fluids  of  the  body  of 
what  has  come  to  be  known  as  the  "hormone  bal- 
ance." 

Disturbances  of  this  balance  are  responsible  for 
most  of  the  functional  disorders  in  women.  This 
is  a  broad  statement,  I  know,  and  it  will  be  ques- 
tioned by  some  who  still  are  certain  that  the  nerv- 
ous system  and  derangements  of  it,  are  responsible 
for  many  functional  gynecological  disturbances. 
However,  it  has  been  stated  by  more  than  one  in- 


102  THE  INTERNAL  SECRETIONS 

vestigator  of  authority  that  the  nervous  system  it- 
self, and  more  especially  the  sympathetic  nervous 
system,  is  under  the  direct  control  of  certain  of  the 
endocrine  organs;  and  the  conclusions  made  by 
Cannon,  of  Harvard,  as  to  the  relation  of  the  emo- 
tions to  adrenal  activity,  indicate  that  the  adrenal 
medulla  is  a  prominent  factor  in  the  causation  of 
many  manifestations  commonly  associated  with 
fear,  rage  or  pain.  Now  the  chromaffin  tissue  of 
the  adrenal  medulla  is  but  an  integral  part  of  the 
endocrine  system,  and  is  just  as  intimately  con- 
nected with  the  other  parts  of  this  system  as  are 
the  thyroid,  pituitary,  ovaries  or  any  other  of  the 
ductless  glands;  hence  if  disorders  which  are  de- 
pendent upon  emotional  disturbances  really  have 
an  internal  secretory  basis,  it  is  obvious  that  very 
few  functional  troubles  in  women  are  not  in  that 
category  of  disturbances  now  being  differentiated 
and  called  "endocrine  disorders."  Practically  all 
such  conditions  are  in  a  greater  or  less  degree 
amenable  to  organotherapeutic  procedures,  and  the 
more  these  are  applied  in  clinical  practice,  the  more 
are  we  convinced  of  the  importance  and  extent  of 
this  comparatively  new  class  of  disorders. 

It  is  difficult  intelligently  to  discuss  a  subject  as 
broad  as  neurasthenia.  First  of  all  it  is  not  really 
an  entity,  but  rather  a  symptom-complex  with  vary- 
ing manifestations.  While  it  is  found  in  both 
sexes,  it  is  much  more  common  in  women,  and  most 
frequently  is  connected  in  some  way  with  one  or 


IN  PRACTICAL  MEDICINE  103 

more  disorders  of  the  sex  apparatus.  When  a  pa- 
tient comes  to  us  with  a  combination  of  symptoms 
which  the  clinical  history  seems  to  connect  with  a 
menstrual  disorder,  deranged  or  misused  repro- 
ductive functions,  climacteric  irregularities  or  a 
general  run-down  condition,  if  there  is  a  nervous 
element  in  the  case — and  in  how  few  is  there  not? 
— it  is  very  easy  to  call  it  neurasthenia. 

As  a  matter  of  fact  it  is  impossible  not  to  have 
neurasthenia  in  patients  who  are  below  par,  for 
when  an  individual  is  asthenic  and  debilitated,  the 
nervous  mechanism  is  likely  to  be  just  as  asthenic 
as  the  muscular  system,  the  eliminative  system  or 
the  endocrine  system;  and  when  we  meet  women 
who  are  hysterical  or  melancholic;  excitable  or 
apathetic;  menstrually  plus  or  minus  (if  I  may  use 
such  a  term) ;  or  are  suffering  in  some  way  as  a 
result  of  an  over-  or  under-activity  of  the  genital 
organism,  we  might  better  consider  them  from  the 
standpoint  of  the  internal  secretions  rather  than  to 
classify  them  as  neurasthenics  and  give  them  tonic 
or  sedative  treatment  according  to  the  exigencies 
of  each  case. 

I  have  come  to  the  conclusion  that  it  is  not  pos- 
sible to  treat  functional  gynecological  disorders  ef- 
fectively without  in  every  case  carefully  consider 
ing  each  individual  from  this  standpoint.  The  duct- 
less glandular  system  in  women  is  as  sensitive  to 
physiologic  impressions  as  the  nervous  system; 
hence  one  must  expect  to  encounter  pluriglandular 


104  THE  INTERNAL  SECRETIONS 

disturbances  very  frequently.  The  principal  rea- 
son that  this  does  not  seem  to  have  been  done  more 
often  is  because  the  subject  has  not  yet  reached 
that  stage  of  stability  which  some  physicians  insist 
upon.  You  know  that  there  are  still  members  of 
our  profession  who  deny  the  "hormone  theory/'  as 
they  like  to  call  it;  and  with  this,  of  course,  they 
virtually  deny  the  feasibility  as  well  as  the  appli- 
cability of  organotherapy.  It  is  to  be  hoped  that 
everyone  present  this  evening  is  safely  out  of  this 
class,  and  that  all  will  admit  with  me  the  probable 
relationship  of  ductless  glandular  disorder  with  the 
majority  of  those  cases  usually  called  "neuras- 
thenics." If  so,  a  few  suggestions  of  a  therapeutic 
nature  may  be  acceptable,  and  the  discussion  which 
follows  doubtless  will  bring  out  considerably  more 
of  practical  value  than  does  this  paper. 

There  is  a  comparatively  small  number  of  women 
whose  neurasthenic  manifestations  are  associated 
with  ovarian  and  menstrual  superactivity.  Their 
periods  are  prolonged  and  excessive,  they  have  so 
little  freedom  from  the  inconveniences  of  menstru- 
ation and  their  economy  is  so  depleted  by  the  undue 
loss  of  blood  and  strength,  that  they  easily  become 
neurasthenic.  Often  they  brood  over  their  condi- 
tion; and,  rarely,  the  onset  of  a  heavy  flow  pros- 
trates them  not  merely  physically  but  mentally.  All 
too  often  these  cases  are  called  "endometritis"  for 
convenience  and  are  treated  surgically  with  medi- 
ocre results;  while  many  might  be  benefited  by  the 


IN  PRACTICAL  MEDICINE  105 

exhibition  of  mammary  extract.  This  substance 
antagonizes  ovarian  activity,  depletes  the  uterine 
vessels  and  is  an  excellent  means  of  controlling 
functional  uterine  hemorrhage.  Incidentally  it  has 
been  given  with  good  results  in  uterine  fibroids,  not 
only  stopping  the  hemorrhage  but,  in  an  encour- 
aging proportion  of  cases,  reducing  the  size  and 
stopping  the  growth  of  the  tumor.  But  this  is  tak- 
ing us  from  the  subject  of  the  evening.  Mammary 
extract  is  given  in  5-grain  doses,  preferably  at 
meals.  Ten  grains  three  times  a  day  is  usually  the 
maximum  and  if  this  is  continued  for  two  or  three 
weeks,  then  omitted  during  the  days  free  from  men- 
strual flow  and  started  again,  and  if  necessary 
pushed,  during  the  flow,  to  be  discontinued  again 
till  the  next  menses  and  given  in  this  manner  for 
two  or  three  months,  the  effects  of  the  increased 
ovarian  activity  will  be  reduced  and  the  benefit  will 
usually  embrace  other  symptoms  than  the  one  for 
which  mammary  therapy  originally  was  instituted. 

A  larger  number  of  neurasthenic  women  exhibit 
the  opposite  pelvic  conditions,  and  suffer  from  de- 
layed or  insufficient  menses.  This  is  but  one  symp- 
tom in  a  chain  of  disorders  due  to  hypoendocrinism 
(hypocrinism) — reduced  internal  secretory  activity 
and  one  which  gives  us  an  excellent  opportunity  to 
apply  the  principles  of  organotherapy,  and  not  only 
remove  the  menstrual  disabilities  but  with  them  the 
associated  neurasthenia.  Such  individuals  are  usu- 
ally   anemic,    insufficiently    nourished    and    toxic. 


106  THE  INTERNAL  SECRETIONS 

Thev  are  flabbv,  often  obese  and  do  not  react  well 
to  the  morning  bath  (which,  by  the  way,  very  few 
of  them  take)  or  to  treatment  of  any  kind.  Their 
cells  are  physiologically  lazy  and  asthenic  (al- 
though they  may  be  mentally  bright  and  despite 
their  troubles  may  attempt  to  be  quite  active  phys- 
ically). Yet  always  associated  with  these  common 
conditions  there  is  a  more  or  less  marked  nervous 
element  which  is  usually  singled  out  and  given  un- 
due prominence  in  the  nomenclature  as  well  as  the 
therapeutics,  for,  of  course,  such  cases  are  obvi- 
ously "typical  cases  of  neurasthenia." 

The  cellular  inactivity  of  such  individuals  almost 
invariably  indicates  a  condition  of  minor  hypothy- 
roidism, in  fact  this  disorder  may  be  the  principal 
basic  cause  of  the  whole  trouble,  for  it  is  surprising 
how  many  times  the  thyroid  may  be  responsible  for 
functional  disorders  of  many  kinds.  (By  the  way, 
this  statement  is  not  made  thoughtlessly;  for  many 
functional  cellular  disabilities  can  either  be  traced 
to  hypothyroidism  or  shortly  after  the  onset  are  ag- 
gravated by  an  associated  thyroid  inadequacy;  and 
while  in  some  cases  other  factors  may  be  predomi- 
nant, to  the  seeing  eye  there  is  usually  a  path  of 
more  or  less  prominence  which  leads  to  the  thyroid 
mechanism).  This  hypothyroidism,  in  turn,  may 
cause  a  reduced  luteal  activity  and  when  it  is  suffi- 
ciently marked  to  be  clinically  evident,  many  of  the 
endocrine  glands  are  already  working  at  half  speed 
or  even  slower.    This  explains  the  good  results  fre- 


IN  PRACTICAL  MEDICINE  107 

quently  obtained  from  pluriglandular  therapy  in 
such  cases,  of  which  more  shortly. 

This  action  is  strictly  speaking  a  reflex  action, 
and  the  use  of  this  term  needs  a  brief  qualification. 
It  may  be  and  probably  is  nervous,  but  it  is  also  and 
more  decidedly  hormonic  in  origin.  The  thyroid 
produces  an  internal  secretion  which  stimulates  the 
ovaries  and  their  corpora  lutea,  hence  a  "reflex" 
influence  of  reduced  thyroid  action  is  a  correspond- 
ingly reduced  luteal  action,  and  so  on.  This  means 
that  there  may  be  cases  of  amenorrhea  of  distinct 
thyroid  origin;  and  it  is  of  interest  to  recall  that 
Prof.  Dalche,  of  Paris,  regards  amenorrhea  and  es- 
pecially dysmenorrhea  in  young  women,  as  defi- 
nitely due  to  thyroid  rather  than  ovarian  disorder. 
He  reports  the  successful  treatment  of  many  cases 
of  this  character  by  giving  thyroid  alone,  the  dose 
usually  being  1  or  2  centigrams  per  day  in  divided 
amounts. 

By  far  the  greatest  number  of  menstrual  neuras- 
thenics, as  well  as  practically  all  sexual  neuras- 
thenias in  women,  have  their  origin  in  a  functional 
derangement  of  the  internal  secretory  portion  of 
the  ovaries.  This,  of  course,  is  the  corpus  luteum, 
although  the  ovarian  stroma  has  been  shown  to 
exert  a  certain  but  minor  influence  of  this  nature. 
Since  the  development  of  a  corpus  luteum  is  sup- 
posed to  be  synchronous  with  the  onset  of  menstru- 
ation, per  contra,  the  absence  or  semi-absence  of 
the  menses  is  often  due  to  a  decreased  production 


108  THE  INTERNAL  SECRETIONS 

of  the  luteal  hormone.  This  disturbs  the  delicate 
hormone  balance,  already  referred  to,  and  is  di- 
rectly concerned  in  bringing  about  certain  neuras- 
thenic manifestations,  at  the  same  time  reflexly 
(hormonically)  producing  a  vicious  circle. 

The  whole  subject  is  being  studied  experiment- 
ally in  several  laboratories  and  many  hundreds  of 
clinical  applications  are  being  made  from  week  to 
week,  although  but  a  small  number  of  them  are  re- 
ported for  the  benefit  of  the  profession.  It  may  be 
said  unequivocally  that  there  is  an  incontestible  re- 
lation between  the  physiologic  action  of  the  corpora 
lutea  and  neurasthenia.  Howard  Kelly  and  C.  H. 
Burnham  of  Baltimore  have  established  this  on  a 
practical  basis  and  have  reported  a  number  of  cases 
of  typical  neurasthenia  in  women,  which  were  suc- 
cessfully treated  with  lutein.  R.  T.  Frank  of  New 
York,  Adam  Leighton  of  Portland,  Me.,  Paul  Car- 
not  of  Paris,  W.  Blair  Bell*  of  Liverpool  and  sev- 
eral others  that  I  might  mention,  have  expressed 
themselves  on  this  subject,  and  we  cannot  but  con- 
clude that  not  only  is  neurasthenia  frequently  due 
to  functional  disturbances  in  the  hormone  produc- 
tion of  the  ovaries,  but  that  it  may  also  respond  fa- 
vorably to  suitable  doses  of  luteal  preparations. 

In  passing  it  may  be  well  to  mention  briefly  a 


*I  feel  it  a  privilege  to  add  here  that  my  friend  Dr.  Blair 
Bell  recently  has  published  a  book  entitled  "The  Sex  Complex" 
(Bailliere,  Tindall  &  Cox.,  London,  or  Wm.  Wood  &  Co.,  New 
York),  in  which  the  relation  of  the  internal  secretions  to  the 
female  economy  is  taken  up  in  a  masterly  and  interesting 
fashion. 


IN  PRACTICAL  MEDICINE  109 

form  of  neurasthenia  accompanied  by  dysmenor- 
rhea in  women  near  the  menopause.  These  cases 
are  usually  obese  and  metabolism  is  invariably  re- 
duced. Lemaire  of  Paris  believes  that  most  cases 
of  this  character  are  due  to  a  disturbed  equilibrium 
between  the  internal  secretory  glands,  and  he 
recommends  in  such  cases  the  administration  of 
combinations  of  thyroid  and  luteal  substances.  In 
his  experience  he  finds  that  this  treatment  not  only 
reduces  the  pain  and  discomfort  at  the  menses,  but 
also  enhances  the  metabolism  and  many  times  con- 
trols the  distressing  neurasthenic  manifestations. 

Another  of  the  ductless  glands  likely  is  con- 
cerned in  many  cases  of  neurasthenia  in  women. 
The  pituitary  body  and  its  various  distinct  parts 
are  not  so  well  understood  as  the  thyroid  or  the 
corpus  luteum;  but  the  hypophysis  is  none  the  less 
a  part  of  the  endocrine  system  and  as  such  exerts 
some  influence  upon  such  a  broadly  extending  com- 
plexity as  neurasthenia.  Neurasthenia  is  not  in- 
frequently a  side-issue  in  cases  of  dyspituitarism 
and  as  we  have  opportunity  to  study  more  closely 
these  relations  in  women  with  pituitary  disease,  we 
will  be  able  to  speak  with  more  authority  on  this 
phase  of  the  subject.  From  a  practical  standpoint 
we  do  know,  however,  that  the  administration  of 
total  pituitary  substance  hasa  beneficial  and  quite 
general  tonic  influence,  especially  in  those  indefi- 
nite, asthenic  cases  where  the  nervous  and  muscu- 
lar efficiency  seems  to  be  especially  deficient.     As 


110  THE  INTERNAL  SECRETIONS 

an  empirical  remedy  in  such  cases,  as  well  as  in 
certain  pluriglandular  insufficiencies,  pituitary  sub- 
stance (whole  gland)  is  helpful  because  of  its  tonic 
action  upon  cardiac,  intestinal  and  uterine  muscles; 
and  while  there  still  may  be  only  slight  scientific 
ground  for  giving  it  in  many  cases,  it  is  of  un- 
doubted clinical  value,  and  when  an  eminent  man 
like  Leonard  Williams,  of  London,  expresses  his 
faith  in  pituitary  as  a  remedy  for  amenorrhea  and 
menstrual  neurasthenias,  I  am  content  to  believe 
without  the  "incontestible  scientific  proof'  that 
some  physicians  still  insist  upon — in  public!  Inci- 
dentally I  would  like  to  ask  how  it  is  possible  to 
establish  a  subject  relating  to  therapeutics  upon 
this  hypothetical  plane  of  indubitability  without  a 
certain  amount  of  clinical  experience;  and  if  we  are 
to  refrain  from  empiricism,  how  are  we  to  progress? 
This  same  Leonard  Williams  has  also  found 
pituitary  of  value  in  those  cases  he  amusingly  calls 
"the  moth-eaten  old  ladies  who  come  out  of  board- 
ing houses  to  go  to  church'';  and  it  will  also  be 
found  useful  in  the  elderly,  inactive,  neurasthenic 
women  who,  perhaps,  are  not  always  found  in  this 
same  rare  category.  In  a  paper  read  before  the 
Royal  Society  of  Medicine,  which  I  had  the  pleasure 
of  hearing  some  years  ago,  Williams  spoke  favor- 
ably of  a  pluriglandular  preparation  called  hormo- 
tone,  which  is  a  combination  of  the  three  glands 
mentioned  this  evening — thyroid,  pituitary  and 
ovaries.  In  my  own  limited  experience  I  have  found 


IN  PRACTICAL  MEDICINE  111 

this  frequently  superior  to  corpus  luteum  alone 
(save  only  in  cases  where  the  ovaries  have  been 
removed  and  cannot  therefore  respond  to  the  homo- 
stimulant  action  of  the  luteal  ingredient) ;  and  it 
has  the  advantage  of  costing  considerably  less,  for 
unfortunately  corpus  luteum  is  still  an  expensive 
remedy  and  the  recent  increased  demand  seems  to 
be  making  the  price  go  up,  rather  than  down,  as 
one  might  presume.  At  all  events  I  have  seen  good 
results  from  this  combination  in  neurasthenia  in 
women. 

In  cases  with  amenorrhea  the  increased  action  of 
the  thyroid  and  ovaries  not  uncommonly  has  re- 
established the  flow  and  associated  nervous  mani- 
festations due  solely  to  the  repression  of  this  func- 
tion, were  also  controlled.  In  the  nervous  mani- 
festations of  the  artificial  menopause,  especially  in 
comparatively  young  women,  it  is  not  so  effective 
unless  corpus  luteum  is  given  with  it,  in  the  pro- 
portion of  5  grains  of  corpus  luteum  to  one  or  two 
tablets  of  hormotone,  three  times  a  day.  In  dys- 
menorrhea occasionally  it  has  stopped  the  pain  al- 
most like  a  sedative  drug,  while  again  in  seemingly 
identical  cases  it  has  seemed  to  be  quite  inert.  (Par- 
enthetically this  is  not  an  uncommon  experience  in 
organotherapeutic  practice.)  One  cannot  always 
depend  upon  similar  results  from  the  same  treat- 
ment in  presumably  similar  cases.  The  influence 
of  these  hormone-bearing  preparations  is  rarely  di- 
rectly due  to  the  action  of  the  principles  they  con- 


112  THE  INTERNAL  SECRETIONS 

tain,  but  rather  to  the  results  of  their  homostimu- 
lant  action;  i.  e.,  to  the  increased  activity  of  the 
glands  which  they  stimulate  and  the  enhanced  hor- 
mone production.  Perhaps  an  explanation  of  this 
somewhat  discouraging  experience  lies  in  lack  of 
persistence,  for  not  always  are  the  ductless  glands 
as  easily  stimulated,  while  in  some  of  the  rapid- 
acting  cases  the  startling  results  are  brought  about 
because  the  missing  but  all  essential  touch  is  given 
to  the  pendulum,  and  it  starts  again. 

In  the  nervous  and  circulatory  disturbances  of 
the  menopause  pluriglandular  therapy  is  worth  try- 
ing, for  these  symptoms  are  in  most  cases  naught 
save  the  natural  results  of  the  removal  of  stimuli  to 
which  the  body  has  accustomed  itself  for  thirty 
years  or  more. 

There  are  other  phases  of  this  subject  which  will 
occur  to  you.  In  some  cases  the  endocrine  element 
will  be  very  apparent  when  one  is  looking  for  it; 
while  in  others  it  is  not  easy  to  demonstrate.  In 
such  cases,  however,  it  is  there  none  the  less  and  I 
prefer  to  imagine  that  this  unnoticed  factor  is  play- 
ing some  minor  role,  and  that  the  more  obvious 
manifestations  of  diagnostic  value  have  not  yet  be- 
come sufficiently  marked  to  be  differentiated. 

In  conclusion,  the  administration  of  thyroid,  cor- 
pus luteum  or  pituitary  gland,  or  combinations  of 
them,  to  my  mind  is  as  rational  a  form  of  the  treat- 
ment of  many  of  the  functional  neuroses  in  women, 
including  neurasthenia,  as  one  could  hope  for.     Of 


IN  PRACTICAL  MEDICINE  113 

course,  such  remedies  do  not  militate  against  the 
hygienic  procedures  or  even  drugs  that  may  seem 
to  be  indicated,  on  the  contrary  one  will  often  find 
that  organotherapy  renders  the  response  to  other 
treatment  much  more  satisfactory. 

In  applying  the  principles  of  endocrinology  in 
the  consideration  and  treatment  of  neurasthenia  in 
women,  we  are  removing  obstacles  and  assisting 
Nature;  and  where  this  is  accomplished  one  can 
expect  with  much  more  confidence  than  otherwise, 
that  Nature  will  be  better  able  to  bring  about  the 
much-to-be-desired  outcome. 


X 

SEX  DISABILITIES  CONSIDERED  AS 
ENDOCRINE  DYSCRASIAS 

EACH  part  of  the  endocrine  system  depends 
upon  and  influences  each  other  part.  Each  of  them 
is  indispensable  to  the  organism,  though  experi- 
mentally it  has  been  shown  that  life  is  not  neces- 
sarily terminated  by  the  removal  of  one  or  more 
of  these  essential  organs,  though  we  know  that  the 
adrenal  glands  and  the  parathyroids  are  quite  nec- 
essary to  life. 

Not  least  in  importance  among  these  "glands  of 
life"  are  the  gonads,  and  while  their  physiological 
importance  to  the  economy  as  a  whole  is  admitted, 
it  sometimes  seems  that  it  is  not  appreciated,  at 
least  in  therapeutics.  There  is  no  longer  a  question 
as  to  the  internal  secretory  capacity  of  both  ovaries 
and  testes,  nor  can  there  be  any  doubt  of  the  im- 
portance of  their  chemical  messengers.  Neverthe- 
less it  is  a  common  thing  to  discover  sex  disabilities 
that  have  not  been  considered  as  endocrine  dys- 
crasias,  and  more  than  often  in  consequence  have 
been  treated  without  success.  The  "bad  name" 
given  to  the  particular  form  of  therapeutics  inaug- 
urated immediately  following  Brown-Sequard's 
epoch-making  announcement  before  the  Paris  Bio- 
logical Society  in  June,  1889,  was  not  deserved  and, 
like  the  baneful  effects  of  gossip,  persisted  long 
after  its  inherent  value  had  been  firmly  established. 
(114) 


IN  PRACTICAL  MEDICINE  115 

To  the  writer  at  least  the  method  of  treatment 
inaugurated  by  Brown-Sequard  is  rational  because 
it  is  resultful.  The  personal  experiences  of  this 
distinguished  savant  must  be  considered  as  well 
founded  for  the  treatment  was  administered  to 
himself  in  a  scientific  laboratory  where  the  study 
of  physiology  was  uppermost  and  under  circum- 
stances most  favorable  to  calm  and  judicious  con- 
sideration of  the  findings.  And  the  experience  of 
Brown-Sequard  has  been  duplicated  time  and  again 
for  over  thirty  years. 

Sex  disabilities  must  needs  be  considered  as  re- 
sulting from  internal  secretory  disorder  because 
the  sex  manifestations  are  so  absolutely  under  the 
regulation  of  the  endocrine  system.  Not  merely  do 
the  gonads  bring  about  their  subtle  influences  upon 
feature,  form  and  function;  but  they  themselves  are 
played  upon  by  the  other  ductless  glands,  and  I  do 
not  think  that  there  is  a  single  endocrine  disturb- 
ance affecting  any  of  the  glands  of  internal  secre- 
tion that  does  not  have  in  its  syndrome  some  direct 
or  indirect  effect  upon  the  gonads  and  their  work. 

The  thyroid,  best  known  of  the  glands  of  internal 
secretion,  certainly  exerts  its  influence  upon  the  de- 
velopment and  functional  value  of  the  ovaries  or 
the  testes,  for  the  cretin  is  never  sexually  developed 
and  the  sufferer  from  myxedema  acquires  with  the 
myxedematous  characteristics  typical  changes  in 
the  sex  manifestations  which  undoubtedly  are  due 
to  the  modified  thyroid  chemistry.    The  lack  of  the 


116  THE  INTERNAL  SECRETIONS 

thyroid  hormone  predicates  gonad  insufficiency.* 
The  opposite  happens  to  be  equally  true,  for  hyper- 
thyroidism is  not  uncommonly  associated  with 
hyperovarism,  menstrual  difficulties  and,  occasion 
ally,  erethism.  Pelvic  congestion  is  not  an  uncom- 
mon accompaniment  of  hyperthyroidism  as  every 
gynecologist  well  knows. 

The  pituitary  gland  is  none  the  less  intimately 
connected  with  the  sex  glands,  and  the  best  known 
forms  of  pituitary  disease  have  as  prominent  clin- 
ical features,  functional  or  even  structural  changes 
in  the  gonads.  Hypopituitarism  is  sometimes 
called  "dystrophia  adiposo-genitalis"  because  the 
dystrophy  makes  itself  so  manifest  in  the  genital 
form  and  function.  Insufficiency  of  the  pituitary 
gland  spells  genital  insufficiency,  while  possibly 
pituitary  excess  may  cause  a  temporary  increased 
genital  function,  though  this  is  not  so  common  as 
in  the  opposite  condition;  and,  too,  it  must  be  re- 
membered that  hyperpituitarism  very  commonly 
metamorphoses  into  hypopituitarism  and  this  may 
account  for  the  asexual  manifestations  occasion- 
ally seen  in  individuals  with  well  defined  changes 
due  to  an  obvious  pituitary  excess. 

The  adrenal  glands  are  also  connected  with  the 
gonads,  though  there  is  not  so  much  clinical  data 
on  this  phase  of  endocrinology  as  in  the  study  of 
the  thyroid  or  pituitary  glands.     Nevertheless  the 


*And  sex  deficiencies  should  lead  one  to  look  for  evidence 
of  thyroid  and  other  endocrine  symptoms. 


IN  PRACTICAL  MEDICINE  117 

profession  is  now  fairly  unanimous  that  certain 
sexual  complications  have  an  adrenal  origin,  for 
instance  the  peculiar  organic  and  functional 
changes  called  "virilism"  in  which  the  female  char- 
acteristics are  supplanted  by  obvious  masculine 
characteristics,  have  been  shown  by  Apert,  Ballet, 
Tuffier  and  others  to  be  the  result  of  organic  ad- 
renal disorder.  On  the  other  hand  Addison's  dis- 
ease is  practically  always  accompanied  by  impo- 
tence. The  functional  form  of  adrenal  insufficiency 
discussed  in  Chapter  VII  may  be  expected  to  be 
accompanied  by  some  sort  of  sex  depression,  for 
the  asthenia  of  hypoadrenia  cannot  well  affect  so 
many  functions — circulation,  muscular  power,  men- 
tal activity,  etc. — without  some  influence  upon  the 
gonads.  I  have  had  several  experiences  which  sup- 
port this  view  and  have  had  a  number  of  illustrative 
cases  brought  to  my  attention.  The  case  of  ovarian 
poisoning  referred  to  on  page  86  is  one.  The  case 
of  shock  following  the  "near  accident"  mentioned 
on  page  74  is  another.  I  heard  of  a  physician 
who  had  been  impotent  for  a  year  or  more  follow- 
ing an  accident,  whose  hormone  balance  had  been 
severely  disorganized  and  whose  blood  pressure 
and  other  clinical  evidences  indicated  a  state  of 
chronic  hypoadrenia.  Tonic  hormone  therapy  re- 
stored this  balance  in  a  short  time.  In  the  chapter 
on  shell  shock  (VI)  I  might  have  added  that  this 
condition  is  practically  always  associated  with  evi- 
dence of  disturbances  in  the  sex  manifestations. 


118  THE  INTERNAL  SECRETIONS 

There  is  much  evidence  in  favor  of  the  sugges- 
tion that  sex  disabilities  may  be  associated  with  or 
due  to  dyscrinism,  and  that  the  adrenal  system,  so- 
called,  is  intimately  functionally  related  with  the 
sex  glands. 

The  relation  of  the  thymus  to  the  sex  glands  is 
now  fairly  well  understood,  and  it  has  been  shown 
that  a  persistent  thymus  is  likely  to  be  the  cause  of 
genital  insufficiency,  for  the  thymus  itself  produces 
a  chemical  antagonist  to  the  gonads  and  as  soon  as 
it  normally  atrophies  just  before  puberty,  the  sex 
glands  are  thus  permitted  to  assert  their  chemical 
or  hormonic  functions. 

Several  of  the  clinical  reports  in  comparatively 
recent  literature  indicate  that  parathyroid  disease 
also  exerts  its  influence  upon  the  sex  glands.  While 
Parkinson's  syndrome  or  paralysis  agitans  is  not 
admitted  by  all  to  be  a  distinct  parathyroid  dis- 
order, there  is  a  good  deal  of  evidence  in  favor  of 
this  position,  and  I  have  encountered  not  merely 
good  results  following  the  parathyroid  method  of 
treatment  of  this  disease,  but  have  seen  the  sex  dis- 
ability which  is  a  part  of  the  syndrome  materially 
modified  for  the  better  following  a  longer  or  shorter 
course  of  parathyroid  treatment. 

At  present  the  pineal  is  not  supposed  to  be  a 
gland  of  internal  secretion  although  from  my  own 
standpoint  it  is  difficult  to  explain  many  of  the  find- 
ings connected  with  epiphyseal  tumors  on  any  other 
basis  than  that  of  internal  secretion.    At  all  events 


IN  PRACTICAL  MEDICINE  119 

hyperpinealism  has  been  shown  to  be  accompanied 
by  a  very  remarkable  early  ripening  of  the  sex 
glands,  and  precocity  both  mentally  and  sexually. 
Whether  this  is  of  endocrine  origin  or  not,  it  is  a 
matter  of  considerable  clinical  interest. 

With  these  briefly  outlined  facts  in  mind,  we  can 
not  but  conclude  that  the  disabilities  of  sex  always 
deserve  consideration  from  an  internal  secretory 
standpoint.  Dysgenitalism  is  dyscrinism,  and  clin- 
ically as  well  as  therapeutically  this  position  can  be 
established  beyond  peradventure.  Many  a  case  of 
obscure  neurasthenia  will  be  found  to  be  accom- 
panied by  a  sexual  neurosis  which  is  really  the  bot- 
tom of  the  whole  matter.  Indeed,  I  am  convinced 
that  much  of  the  success  following  pluriglandular 
therapy  as  outlined  elsewhere,*  is  largely  due  to  a 
re-establishment  of  an  unappreciated  dysgenital- 
ism. Many  forms  of  organotherapy  are  known  to 
affect  genital  function.  Thyroid  extract  has  been 
used  time  and  again  to  control  menstrual  disorders. 
Its  use  has  been  equally  efficacious  in  re-establish- 
ing a  more  nearly  normal  sexual  development  and 
activity  in  individuals  suffering  from  both  major 
and  minor  thyroid  insufficiencies.  The  orthodox 
treatment  of  the  Froehlich  syndrome  (dystrophia 
adiposo-genitalis)  is  pituitary  feeding,  and  one  of 
the  therapeutic  results  is  a  favorable  modification 
of  sexual  development  and  function.  In  fact  pitui- 
tary feeding  is  beginning  to  be  used  with  moder- 


*See  Chapters  V,  VI,  VIII  and  IX. 


120  THE  INTERNAL  SECRETIONS 

ately  good  results  in  sexual  insufficiencies  not  nec- 
essarily connected  with  well  marked  pituitary  dis- 
ease, and  quite  recently  Stelwagen  (N.  Y.  Med. 
Jour.,  1917,  ciii,  879)  reports  the  successful  treat- 
ment of  a  number  of  cases  of  functional  impotence 
with  15  or  more  grains  of  anterior  pituitary  gland 
administered  daily  for  a  period.  It  is  granted  that 
this  is  a  preliminary  report,  but  at  least  it  is  a  sug- 
gestive experience  as  we  consider  the  particular 
subject  under  discussion. 

Quite  the  most  important  phase  of  organother- 
apy in  dysgenitalism  is  the  use  of  extracts  of  or- 
gans corresponding  to  those  affected — the  ovaries 
or  testes,  as  the  case  may  be. 

Corpus  luteum  has  established  itself  as  a  stand- 
ard remedy  in  many  functional  genital  disturbances 
in  gynecological  practice,  and  its  value  is  referred 
to  elsewhere  in  this  book;  but  somehow  or  another 
the  corresponding  treatment  in  the  male  still  re- 
mains "under  a  cloud/'  The  physician  who  would 
champion  luteal  preparations  without  a  question, 
says  little  about  the  use  of  testicular  preparations; 
and  there  is  a  very  obvious  question  about  this  in 
the  minds  of  the  majority  of  the  profession. 

Despite  this  I  have  the  utmost  confidence  in  this 
phase  of  organotherapy.  I  believe  that  Brown- 
Sequard's  findings  were  based  upon  good  physiol- 
ogy and  were  not  overstated,  and  while  we  will 
grant  that  there  undoubtedly  were  many  overstate- 
ments in  the  nineties,  especially  by  the  aggressive 


IN  PRACTICAL  MEDICINE  121 

quacks  who  seized  upon  Brown-Sequard's  reports 
to  fleece  their  gullible  patients,  this  does  not  change 
the  fundamental  basis  of  reason  for  testicular  or- 
ganotherapy. 

If  functional  impotence  in  the  male  as  well  as  in 
the  female  is  considered  in  the  light  of  an  endocrine 
dyscrasia,  there  is  more  hope  of  a  successful  out- 
come than  from  all  the  electrical,  mechanical  and 
psychotherapeutical  procedures  combined.  The 
principle  of  homostimulation  oft  referred  to  in  my 
writings  applies  just  as  much  to  the  gonads  as  to 
the  thyroid,  pituitary  or  any  other  gland  of  in- 
ternal secretion,  and  the  clinical  results  following 
the  use  of  Didymin,  Sequarine,  Hormotone,  or  the 
Roberts-Hawley  Lymph,  or  any  other  preparation 
calculated  to  stimulate  the  sex  glands  to  a  greater 
functional  activity,  are  based  upon  good  physiology 
and  sound  reasoning,  many  statements  to  the  con- 
trary, notwithstanding.  This  is  not  the  place  for 
case  reports.  I  have  mentioned  one  or  two  previ- 
ously and  could  extend  the  list  materially. 

Let  us  consider  for  a  moment  the  philosophy 
of  the  last  of  these  proprietaries.  Unnumbered 
cases  of  so-called  "incompetence"  have  been  treated 
with  this  lymph.  I  have  personally  used  it  in  my 
practice  and  am  certain  that  this  homostimulant 
action  is  the  physiological  explanation  of  the  good 
results  that  one  can  expect  to  secure  following  its 
judicious  use  in  cases  of  this  character.  I  am  equally 
convinced  that  the  empirical  administration  of  the 


122  THE  INTERNAL  SECRETIONS 

preparation  Hormotone,  or  Tabloid  Mixed  Glands, 
in  dysgenitalism  is  active  through  the  augmented 
internal  secretory  activity  of  the  gonads  which  thus 
may  be  brought  about. 

The  beneficial  effects  from  this  kind  of  treat- 
ment seem  to  originate  from  the  augmented  gonad 
activity  for  this  alone  is  sufficient  to  increase  met- 
abolism, to  create  force  (the  testicular  hormone  has 
been  called  "a  dynamogenic  hormone")  and  to 
start  up  a  greater  degree  of  functional  activity  in 
the  other  interrelated  endocrine  organs.  This  ac- 
counts for  the  unusual  effects  that  have  been  re- 
ported following  the  use  of  the  R-H  Lymph  in  very 
chronic  and  much  treated  cases;  as  well  as  the  more 
direct  effects  on  impotence  and  hypogonadism. 

I  realize  that  statements  such  as  the  foregoing 
are  open  to  criticism  and  that  they  will  be  criticised 
just  as  similar  ones  have  been  critized  for  thirty 
years,  but  the  opinions  of  critics  count  for  naught 
as  compared  with  the  opinions  of  satisfied  patients; 
and  nothing  can  shake  my  belief  that  one  is  more 
likely  to  accomplish  the  desired  therapeutic  ends  in 
the  treatment  of  sexual  disabilities  if  they  are  con- 
sidered as  endocrine  dyscrasias  and  treated  as  such. 


XI 

THE   RELATION   OF  THE   INTERNAL   SE- 
CRETIONS TO  RHEUMATISM  AND 
THE  RHEUMATIC  DIATHESIS 

RHEUMATISM  and  the  rheumatic  diathesis 
are  conditions  concerning  which  the  medical  pro- 
fession holds  numerous  and  widely  differing  views. 
The  literature  regarding  the  various  phases  of 
rheumatism  is  as  extended  as  it  is  contradictory. 
The  unsuspecting  reader  frequently  is  led  into  a 
morass  of  differing  conceptions  from  which  it  is 
not  always  the  easiest  thing  to  extricate  himself. 

Some  writers  insist  that  "rheumatism,"  and  by 
that  they  usually  include  the  varying  disorders 
which  have  been  classed  under  this  name,  is  a  mani- 
festation of  digestive  trouble  pure  and  simple;  cor- 
rect the  digestion  and  the  rheumatism  will  be  auto- 
matically taken  care  of. 

Others  insist  that  it  is  essentially  the  result  of 
an  imperfect  mineral  metabolism  and  assure  the 
reader  that  recourse  to  certain  inorganic  neutral- 
izing remedies  will  quickly  bring  conviction  regard- 
ing the  correctness  of  this  view. 

Still  others  assert  that  there  is  a  bacterial  origin, 
not  only  for  the  obviously  infective  forms  of  rheu- 
matism, but  for  all  of  them;  and  that  the  successful 
treatment  of  this  disorder  is  not  complete  without 


Prepared  for  a  "Special  Rheumatism  Number"  of  American 
Medicine  (New  York),  published  June,  1915. 

(123) 


124  THE  INTERNAL  SECRETIONS 

at  least  the  addition  of  procedures  based  upon  its 
"undoubted  microbic  origin." 

Much  has  been  written  regarding  the  relation  of 
uric  acid  to  the  rheumatic  diathesis  and  opinions 
seem  to  be  veering  away  from  the  statements  so 
ably  presented  by  Dr.  Alexander  Haig.  In  a  recent 
communication  (Interstate  Med.  Jour.,  April,  1915) 
Goodman  aptly  remarks  that:  "The  uric  acid  the- 
ory is  at  present  tottering  on  its  unstable  founda- 
tions and  we  are  growing  more  and  more  inclined 
to  the  view  that  not  uric  acid,  but  rather  disturb- 
ances of  intermediary  purin  metabolism,  are  at  the 
root  of  the  evil." 

Looking  at  this  problem  from  the  standpoint  of 
an  average  physician,  it  is  altogether  probable  that 
there  is  an  element  of  truth  in  all  of  the  theories 
regarding  rheumatism  and  that  the  statements 
which  serve  as  a  prelude  to  this  article  are  all  cor- 
rect to  a  certain  degree.  None  can  deny  that  rheu- 
matism in  the  majority  of  instances  exhibits  as  one 
of  its  most  constant  manifestations  a  disturbance 
of  metabolism,  and  considerable  evidence  is  accru- 
ing to  indicate  that  not  a  few  of  these  cases  have 
as  the  original  basis  of  the  trouble  an  obscure  in- 
fective process  which  may  never  be  so  obvious  as 
to  direct  attention  to  itself,  but  is  only  brought  to 
light  following  the  empiric  use  of  stock  vaccines 
given  with  the  expectation  that  this  unnoticed  in- 
fection may  be  present.  In  such  cases  (and  Sher- 
man, of  Detroit,  has  frequently  directed  attention 


IN  PRACTICAL  MEDICINE  125 

to  the  importance  of  this  class)  the  diagnosis  is 
often  made  by  the  clinical  results  of  the  empirical 
treatment  and  it  may  be  stated  in  unqualified  terms 
that  many  of  the  chronic  rheumatic  affections  are 
of  bacterial  origin,  even  though  they  may  show 
none  of  the  typical  findings  of  obviously  infective 
cases. 

The  manifestations  of  the  rheumatic  diathesis 
are  too  frequently  associated  with  digestive  dis- 
turbances for  the  consistent  physician  to  deny  the 
intimacy  of  this  relation,  and  it  is  not  an  uncom- 
mon thing  for  dietetic  regulation,  with  attention  to 
the  inevitable  defective  elimination  resulting  from 
disturbed  digestive  activity,  to  bring  about  a  com- 
plete control  of  the  rheumatic  phenomena.  Certain 
it  is  that  the  excessive  amounts  of  protein  which 
are  so  commonly  eaten  combine  with  other  factors 
to  bring  about  the  metabolic  chaos  which  is  so  usu- 
ally called  rheumatism.  Parenthetically,  it  might 
be  remarked,  these  persons  are  not  suffering  from 
the  results  of  mineral  excess,  although  the  labora- 
tory evidence  may  seem  to  indicate  this;  rather 
they  are  undergoing  their  tortures  because  of  a 
lack  of  the  natural  mineral  elements — the  vegetable 
alkalies — which  the  body  needs,  and  which  they 
could  just  as  well  have  if  their  diet  included  more 
of  such  articles  as  potatoes,  greens  and  cereals,  and 
less  meat. 

Whether  or  no  the  initial  cause  is  dietetic  or  bac- 
terial in  origin  there  can  be  no  doubt  that  all  forms 


126  THE  INTERNAL  SECRETIONS 

of  rheumatism  are  evidences  of  essential  changes 
in  the  chemistry  of  the  body  and,  this  being 
granted,  should  not  the  regulators  of  metabolism 
be  considered  both  in  the  etiology  as  well  as  in  the 
treatment  of  the  various  forms  of  this  disorder? 

It  should  be  quite  unnecessary  to  lend  emphasis 
to  the  importance  of  the  glands  of  internal  secre- 
tion as  regulators  of  the  functions  of  the  body.  The 
hormones  not  only  control,  but  correlate  these  vari- 
ous cell  activities,  and  their  work  is  so  closely  con- 
nected with  the  factors  which  are  concerned  in  the 
reaction  of  the  body  to  the  causes  of  rheumatism, 
as  well  as  to  the  attempts  made  to  cure  this  condi- 
tion, that  the  physician  who  considers  the  relation 
of  the  internal  secretory  glands  and  their  hormones 
to  rheumatism  is  more  likely  to  solve  some  of  its 
mysteries  than  the  one  who  overlooks  them  en- 
tirely. 

It  is  remarkable  how  close  a  relationship  may  be 
discovered  between  certain  of  the  ductless  glands 
and  the  symptoms  which  have  come  to  be  consid- 
ered pathognomonic  of  rheumatism.  Presuming 
for  a  moment  that  the  various  manifestations  of  the 
rheumatic  diathesis  are  toxic  in  origin,  is  not  de- 
toxication  essentially  controlled  by  certain  of  the 
endocrine  glands? 

If  the  infective  origin  of  rheumatism  is  admitted 
to  be  the  most  frequent  or  important,  then  we  must 
also  admit  that  certain  of  these  remarkable  organs 
are  responsible  for  the  production  of  the  protective 


IN  PRACTICAL  MEDICINE  127 

measures  which  the  body  automatically  brings  into 
play  in  infections.  Sir  Almroth  Wright  himself 
insists  that  all  the  substances  concerned  in  the  con- 
trol of  infections  must  be  considered  as  products 
of  the  internal  secretory  organs. 

If  functional  digestive  disturbances  are  the  most 
common  basis  for  this  condition,  then  it  is  proper 
to  consider  the  relation  of  the  alimentary  hormone, 
secretin,  to  this  disease  and,  where  digestive  in- 
sufficiencies are  manifestly  present,  recourse  be 
had  to  the  use  of  secretin  as  a  remedy,  for  I  am 
thoroughly  convinced  of  its  value  as  a  physiologic 
means  of  stimulating  lazy  or  inactive  digestive 
glands,  statements  to  the  contrary  notwithstand- 
ing. So  whether  rheumatic  conditions  are  purely 
metabolic  in  origin,  or  whether  they  are  due  to 
micro-organisms,  or  to  indigestion,  we  must  not 
belittle  the  fact  that  in  any  event  there  must  be  a 
role  that  the  internal  secretory  organs  play  which 
favors  their  prevention  as  well  as  the  cure. 

Under  the  present  circumstances  it  would  be 
quite  difficult  to  consider  this  from  the  protective 
or  prophylactic  standpoint.  Rheumatism  is  too  in- 
sidious a  disease.  Its  onset  is  of  such  a  nature  that 
it  is  not  appreciated  until  one  or  more  of  the  more 
definite  manifestations — joint  pain,  immobility, 
swelling,  etc., — brings  the  patient  to  his  physician. 
We  can,  however,  make  good  use  of  this  informa- 
tion in  the  diagnosis  and  treatment  of  rheumatic 
conditions.     For  example,  too  often  the  orthodox 


128  THE  INTERNAL  SECRETIONS 

treatment  with  salicylates  or  other  neutralizing 
agents,  does  not  give  the  desired  degree  of  results, 
or  merely  tides  the  patient  over  whilst  the  dis- 
turbed chemical  conditions  are  under  the  influence 
of  the  drugs  or  measures  used.  After  a  longer  or 
shorter  time  the  patient  has  a  recurrence  and  un- 
fortunately, too  often  it  is  more  severe  than  the 
initial  attack.  In  such  cases  the  knowledge  that 
the  ductless  glands  may  be  frequently  concerned 
in  rheumatism  will  enable  the  physician  to  con- 
sider the  case  from  a  slightly  different  angle,  one 
which  I  regret  to  say  is  rarely  taken  by  the  medical 
profession,  and  this  new  viewpoint  may  facilitate 
the  control  of  future  manifestations.  It  will  also 
open  up  the  possibilities  of  certain  forms  of  or- 
ganotherapy which,  rightly  applied,  may  materially 
influence  the  response  of  the  organism  to  the  other 
usual  therapeutic  procedures.  Right  here  it  should 
be  emphasized  that  organotherapy  is  not  recom- 
mended as  the  sine  qua  non  in  the  treatment  of 
rheumatic  affections.  Far  be  it  from  such,  but  as 
an  important  adjuvant  and  a  phase  worthy  of  con- 
sideration it  deserves  considerably  more  attention 
than  it  has  previously  received,  as  may  shortly  ap- 
pear. 

Leopold  Levi,  of  Paris,  insists  that  the  thyroid 
is  quite  intimately  connected  with  both  the  cause 
and,  in  certain  cases,  the  successful  treatment  of 
various  joint  conditions,  not  excluding  the  most  se- 
rious form,  arthritis  deformans,  and  in  the  intro- 


IN  PRACTICAL  MEDICINE  129 

duction  to  his  recent  book  ("La  Petite  Insuffisance 
Thyroidienne  et  son  Traitement")  he  makes  the  fol- 
lowing statement:  "Therapeutics  is  very  helpful 
in  the  study  of  minor  hypothyroidism  for  it  reveals 
several  stigmata  of  this  condition  which  otherwise 
might  be  overlooked.  For  example,  in  March,  1905, 
we  made  the  first  application  of  thyroid  therapy, 
aside  from  the  treatment  of  myxedema,  in  a  sub- 
ject suffering  with  chronic  rheumatism  compli- 
cated with  psoriasis.  The  first  noted  effect  con- 
sisted in  an  increase  in  the  appetite;  the  second  re- 
sult was  a  reduction  in  the  marked  feeling  of  cold 
which  happened  to  be  present  (this  sufferer  was 
astonishingly  cold  and  lived  in  a  degree  of  heat  that 
was  altogether  preposterous).  Strangely  enough 
the  thyroid  therapy  made  a  marked  diminution  in 
this  pecularity  and  also  benefited  the  rheumatism. 

"The  form  of  treatment  applied  in  other  cases  of 
chronic  rheumatism  also  directed  our  attention  to 
a  certain  degree  of  benefit  upon  constipation. "  Else- 
where in  the  same  book  the  author  connects  thyroid 
disturbances  with  rheumatic  manifestations  and 
quotes  a  large  number  of  reports  to  the  effect  that 
"the  reality  of  the  thyroid  causes  of  chronic  rheu- 
matism is  incontestable.  Its  existence  depends  in 
many  cases  on  thyroid  lesions." 

Chronic  rheumatism  is  quite  common  in  subjects 
presenting  signs  of  hypothyroidism  and  it  is  well 
known  that  rheumatic  manifestations  may  be  asso- 
ciated with  or  aggravated  by  incidents  in  the  meno- 


130  THE  INTERNAL  SECRETIONS 

pause.  Frequently  rheumatic  manifestations  fol- 
low thyroid  atrophy  due  to  pathological  conditions 
or  following  thyroidectomy  for  Graves's  disease, 
but  the  most  important  proof  is  the  fact  that  the 
use  of  thyroid  extract  in  many  cases  ameliorates 
rheumatic  manifestations. 

Thyroid  therapy  may  be  applied  frequently  in 
the  treatment  of  various  forms  of  arthritis  with 
very  good  success.  There  are  a  number  of  papers 
recording  and  attempting  to  explain  its  remarkable 
results  in  various  forms  of  chronic  rheumatism. 
Probably  the  most  comprehensive  of  all  these  com- 
munications is  that  of  Leopold  Levi  who  reports 
three  hundred  cases  treated  under  his  direction  dur- 
ing a  period  of  eight  years.  This  investigator,  who 
is  well  known  to  those  who  have  read  the  litera- 
ture on  the  thyroid  gland,  differentiates  a  form  of 
rheumatism  which  is  due  to  what  he  terms  thyroid 
instability.  The  disease  is  found  in  relatively  young 
persons,  is  only  slightly  deforming,  and  usually  af- 
fects the  smaller  joints.  It  seems  to  progress  by 
fits  and  starts.  In  these  cases  the  joint  disturb- 
ances are  by  no  means  the  only  troubles.  Occa- 
sionally there  are  other  manifestations  of  thyroid 
disorder  sometimes  evidently  due  to  increased  thy- 
roid activity  and  at  other  times,  the  majority  of 
cases  it  may  be  noted,  the  result  of  decreased  thy- 
roid activity. 

The  manner  in  which  this  form  of  rheumatism 
responds  to  treatment  varies  considerably  with  the 


IN  PRACTICAL  MEDICINE  131 

associated  manifestations.  In  the  juvenile  form, 
where  there  is  no  very  serious  deformity,  the  re- 
sponse to  treatment  is  good,  and  while  the  serious 
chronic  and  so-called  "incurable"  cases  do  not  re- 
spond as  rapidly  to  this  treatment,  there  is  no 
doubt  that  persistent  thyroid  therapy  causes  a  very 
decided  benefit.  Levi  concludes  that  in  many  cases 
of  chronic  rheumatism  thyroid  extract  is  "a  pre- 
cious remedy,"  securing  an  average  of  results  that 
is  very  encouraging,  and  occasionally  producing 
astonishing  changes  for  the  better.  According  to 
this  writer:  "Thyroid  therapy  should  be  placed  in 
the  first  rank  of  the  therapeutic  armamentarium  in 
the  treatment  of  chronic  rheumatism."  He  recom- 
mends a  daily  dose  ranging  from  .05  to  .30  grammes 
(1  to  S  grains)  in  divided  doses.  The  average  is 
VA  to  3  grains  per  day  and  it  must  be  continued 
for  as  long  as  six  months. 

The  mechanism  of  the  action  of  thyroid  extract 
in  certain  conditions  has  for  some  time  been  in 
doubt;  and  this  is  especially  true  as  far  as  its  influ- 
ence in  rheumatism  has  been  concerned.  This  ex- 
tract, above  all  others,  has  been  considered  one  of 
the  best  means  of  enhancing  cell  activities  and  in- 
creasing the  metabolic  exchanges.  Since  the  met- 
abolism in  rheumatism  is  much  below  par,  any  ad- 
vantage that  accrues  from  ^thyroid  therapy  might 
be  considered  as  due  to  this  effect  upon  the  cells. 

A  scientific  explanation  of  this  may  be  gathered 
from  some  interesting  experiments  by  Slosse  who 


132  THE  INTERNAL  SECRETIONS 

was  professor  of  physiology  at  the  University  of 
Brussels  before  the  war.  He  has  carried  out  a  num- 
ber of  experiments  both  in  the  laboratory  and  in 
the  clinic  to  connect  the  disturbances  of  nitrogen- 
ous metabolism  with  the  work  of  the  ductless 
glands  and  as  a  result  of  his  investigations  he  states 
that  under  normal  circumstances  the  thyroid  gland 
secretes  a  "hormone  de  desamination" — a  deamin- 
izing  hormone — which  influences  the  nitrogenous 
exchanges  and  when  deficient  causes  a  reduction  of 
the  power  of  the  cells  throughout  the  whole  organ- 
ism to  split  up  the  albuminoid  substances,  espe- 
cially the  nucleo-albuminoids,  from  which  uric  acid 
and  other  substances  of  the  purin  group  are  formed. 
Theoretically  then,  the  enhancement  of  thyroid  ac- 
tion should  favor  nitrogenous  metabolism,  and  a 
large  series  of  urinalyses  made  by  Slosse  and  his 
associates  substantiates  this.  The  favorable  clin- 
ical experiences  which  have  been  recorded  by  a 
number  of  French  writers  in  a  measure  may  be  ex- 
plained by  these  findings. 

There  is  another  form  of  chronic  rheumatism 
somewhat  similar  to  that  which  reacts  to  thyroid 
therapy.  Like  it,  it  is  of  endocrine  origin,  but  in- 
stead of  being  due  to  thyroid  insufficiency,  it  is  a 
result  of  ovarian  insufficiency.  This  is  the  rheuma- 
tism which  appears  in  women  after  the  menopause 
and  it  may  be  quite  possible  that  its  etiology  is 
partly  due  to  thyroid  disturbances.  At  least  it  re- 
acts more  quickly  to  luteal  therapy,  especially  if 


IN  PRACTICAL  MEDICINE  133 

this  procedure  is  applied  early  in  the  course  of  the 
disease.  Dalche  reports  that  the  administration 
of  ovarian  substance  has  given  very  good  results 
in  such  cases,  and  in  suitable  cases  he  occasionally 
combines  thyroid  and  luteal  substance. 

It  is  difficult  definitely  to  state  which  case  of 
rheumatism  is  of  thyroid  origin  and  which  is  not. 
According  to  Leopold  Levi  and  de  Rothschild  the 
only  way  to  answer  this  question  is  empirically  to 
apply  thyroid  extract,  and  in  explanation  of  this 
they  may  be  quoted  as  follows :  "From  the  prac- 
tical point  of  view,  in  all  forms  of  rheumatism  in 
which  the  cause  is  unknown,  it  is  an  advantage  to 
apply  thyroid  therapy.  In  such  cases  there  will  be 
more  chance  of  results  if  the  subject  is  young,  if 
the  rheumatism  is  accompanied  by  subacute  ex- 
acerbations, and  if  there  is  only  slight  deformity. 
In  those  cases  where  there  is  a  decided  thyroid  in- 
fluence the  initial  results  will  be  rapid,  sometimes 
immediate.  If  the  treatment  does  not  act  immedi- 
ately, it  is  advisable  to  vary  the  doses,  sometimes 
reducing  them  and  giving  the  remedy  for  a  longer 
period.  There  is  no  doubt  that  this  medication  may 
render  very  great  service  in  the  treatment  of  cer- 
tain rheumatics,  without  exposing  them  to  the  least 
danger."  Of  course  Leopold  Levi  looks  at  every 
disease  from  the  standpoint  of  its  relation  to  the 
thyroid  gland — he  has  been  called  "thyroid  mad" 
— but  the  fact  remains  that  he  and  his  associate, 
Baron  Henri  de  Rothschild,  are  successfullv  treat- 


134  THE  INTERNAL  SECRETIONS 

ing  scores  of  cases  at  their  hospital  with  thyroid 
extract. 

The  thymus  is  another  gland  which  seems  to  be 
connected  in  some  way  with  the  joint  manifesta- 
tions of  rheumatism  and  several  references  have 
appeared  in  the  literature  in  the  last  few  years  ex- 
tolling the  value  of  thymus  extract  in  these  chronic 
joint  conditions. 

Naturally,  it  is  not  always  possible  to  cure  the 
disease — far  be  it  from  me  to  hint  anything  as  defi- 
nite as  this — but  according  to  Nathan  the  first  and 
most  important  beneficial  change  due  to  the  thy- 
mus medication  is  a  reduction  in  the  pain  present, 
and  later,  provided  the  case  responds  to  the  treat- 
ment, there  is  an  increased  mobility  as  well  as  a 
general  betterment  of  the  nutrition  and  health. 

It  is  not  yet  possible  to  expain  why  thymus  medi- 
cation does  this  and  in  what  mysterious  manner 
these  results  are  brought  about,  but  we  know,  at 
least,  that  in  early  life  the  thymus  controls  in  a 
considerable  degree  the  mineral  metabolism,  for 
one  recalls  that  thymectomy  causes  a  remarkable 
softening  of  the  bones  and  an  obvious  disturbance 
of  mineral  metabolism.  It  may  be,  therefore,  that 
there  is  a  principle  in  thymus  extract  which  favors 
the  re-establishment  of  the  disordered  metabolism 
of  calcium  salts  which  is  undoubtedly  a  factor  in 
these  rheumatic  cases,  and  that  the  benefit  is  due 
solely  to  this.  Suffice  it  to  say  that  in  the  treat- 
ment of  arthritis  deformans  Nathan  recommends 


IN  PRACTICAL  MEDICINE  135 

15  to  30  grains  of  thymus  substance  three  times  a 
day  given  for  weeks  or  months  and  some  very  en- 
couraging results  have  been  reported. 

In  conclusion  let  us  remember  the  intimate  rela- 
tion of  the  ductless  glands  to  metabolism,  the  un- 
doubted connection  between  rheumatism  and  meta- 
bolic disturbances  and,  therefore,  the  possibilities 
of  organotherapy  as  a  meritorious  adjunct  in  the 
treatment  of  certain  forms  of  rheumatism. 


XII 

THE  RELATION  OF  THE  THYROID  GLAND 

TO  EPILEPSY 

THE  study  of  the  glands  of  internal  secretion, 
now  being  taken  up  with  avidity  on  all  sides,  bids 
fair  to  outrival  many  other  phases  of  the  study  of 
medicine.  Endocrinology  has  more  to  do  with  the 
really  obscure  and  difficult  problems  of  internal 
medicine  than  many  have  yet  appreciated;  and  as 
our  study  becomes  more  thorough  we  are  realizing 
the  extremely  intimate  relation  between  the  endo- 
crine organs  and  practically  every  phase  of  physio- 
logical activity.  We  are  learning  to  appreciate  as 
never  before  the  importance  over  all  of  the  body  of 
the  chemical  effects  produced  by  the  hormones 
from  these  glands. 

To  me  the  most  interesting  and  recent  work  on 
so-called  "idiopathic  epilepsy"  (the  only  form  of 
epilepsy  referred  to  in  this  paper)  is  that  of  C.  A.  L. 
Reed,  (1)  of  Cincinnati,  whose  several  communi- 
cations have  emphasized  three  important  consid- 
erations: 1st,  that  intestinal  stasis  is  almost  with- 
out exception  present  in  epilepsy;  2nd,  that  a  prom- 
inent result  of  the  associated  toxemia  is  a  varying 
degree  of  acidosis  which  produces  a  condition  of 
edema  of  the  brain  to  which  a  part,  at  least,  of  the 


Reprinted    from    The    Lancet-Clinic    (Cincinnati),   July   29, 
1916. 

(136) 


IN  PRACTICAL  MEDICINE  137 

characteristic  manifestations  of  epilepsy  are  due; 
and  3rd,  that  in  operating  in  the  manner  of  Lane 
on  cases  with  pronounced  intestinal  stasis,  a  marked 
infiltration  of  the  peritoneal  and  mesenteric  glands 
is  usually  encountered,  and  that  from  these  glands 
an  organism,  named  by  Reed  the  epileptococcus, 
frequently  may  be  isolated. 

Though  I  do  not  question  the  findings  of  such  an 
authority,  I  may  be  permitted  to  have  an  opinion 
as  to  the  fundamental  causation  of  the  stasis,  the 
acidosis,  the  edema  and  the  glandular  enlargement. 
For  the  moment  I  am  not  interested  in  the  bacte- 
rial findings  and  the  suggestion  that  we  may  event- 
ually work  out  a  vaccine  therapy  for  this  disease. 

I  believe  that  in  every  case  of  epilepsy  there  is  a 
distinct  endocrine  element  which  is  present  and 
prominent  much  more  frequently  than  has  been  ad- 
mitted in  the  literature  on  the  subject.  This  will 
be  discovered  to  be  as  early  and  constant  a  clinical 
manifestation  as  any  others  with  which  we  are  bet- 
ter acquainted  at  present. 

The  principal  organ  of  internal  secretion  in- 
volved is  undoubtedly  the  thyroid  gland,  although 
others,  notably  the  pituitary,  gonads  and  parathy- 
roids, have  been  connected  with  the  clinical  find- 
ings of  epilepsy. 

It  may  be  well  to  reiterate  some  facts  concerning 
the  relation  of  the  thyroid  to  the  picture  of  intesti- 
nal stasis.  The  man  to  whom  we  are  indebted  for 
first  directing  our  attention  to  the  minor  form  of 


138  THE  INTERNAL  SECRETIONS 

thyroid  insufficiency,  Eugene  Hertoghe,  of  Ant- 
werp, and  who  is  still  the  leading  student  in  this 
line,  called  particular  attention  to  a  syndrome 
identical  with  that  so  prominently  brought  to  the 
fore  by  Sir  Arbuthnot  Lane,  and  did  it  nearly 
twenty  years  ago!  Quoting  from  a  recent  resume 
of  his  work  (2)  on  "chronic  benign  thyroid  insuffi- 
ciency" or  "myxedeme  fruste,"  we  read: 

"The  entire  gastro-intestinal  system  reacts  very 
strongly  to  the  infiltration  of  its  elements,  whether 
muscular,  nervous,  secretory  or  mucous.  Infiltra- 
tion of  the  muscular  tissues  induces  peristaltic  pa- 
resis, leading  to  retention  of  waste  materials  with 
consequent  fermentation  and  constipation.  In  deli- 
cate subjects  with  weak  abdominal  walls  this  re- 
sults in  ptosis  of  the  viscera,  notably  of  those  or- 
gans which  are  most  heavily  loaded,  namely,  the 
stomach  and  large  intestine.  .  .  .  Imperfect  in- 
testinal drainage  gives  rise  to  intestinal  toxemia, 
which  reacts  upon  the  already  enfeebled  thyroid 
and  intensifies  the  prevailing  conditions  of  inade- 
quacy. As  a  matter  of  fact,  many  of  the  symptoms 
attributed  by  Lane  to  chronic  intestinal  stasis  are 
identical  with  those  which,  since  1899,  I  have  in- 
cluded in  the  symptom-complex  of  benign  chronic 
subthyroidism.  These  are  hypothermia,  uncon- 
trollable headache,  rheumatoid  pain  and  neuralgia, 
mental  depression,  dyspnea,  asthmatic  attacks,  pre- 
mature grayness  and  baldness,  dental  caries,  chole- 
lithiasis and  brownish  pigmentation  of  the  skin." 


IN  PRACTICAL  MEDICINE  139 

It  should  not  be  difficult  to  demonstrate  a  fur- 
ther relation  between  the  thyroid  and  epilepsy.  The 
insignificant,  but  none  the  less  important,  signs  of 
the  slighter  form  of  dysthyroidism  are  very  com- 
monly found  in  epilepsy,  occasionally  one  or  two 
of  them  being  very  well  marked,  or  again,  several 
of  them  together  but  not  especially  definite  or  ob- 
vious. This  is  the  usual  reason  that  the  thyroid 
element  is  overlooked;  but  when  one  is  careful, 
some  of  these  signs  will  be  found.  The  permanent 
or  transitory  edema  or  infiltration  of  various  tis- 
sues results  in  such  widely  differing  symptoms  as 
nasal  obstruction,*  changes  in  the  voice,  headache, 
migraine,  a  dry,  rough  skin,  thinning  of  the  hair 
and  especially  the  outer  third  of  the  eyebrows,  cold- 
ness of  the  extremities,  abnormal  chilliness,  dull- 
ness and  backwardness,  menstrual  disorders,  etc. 

These  symptoms,  together  with  those  mentioned 
in  the  above  quotation  from  Hertoghe,  include  a 
majority  of  the  clinical  findings  of  hypothyroidism. 
While  it  is  not  possible  here  to  go  into  the  whole 
subject,  we  must  mention  the  frequency  of  dys- 
crasias  in  other  ductless  glands  in  epileptics,  espe- 
cially of  the  gonads,  for  it  is  well  established  that 
there  is  a  distinct  connection  between  puberty  and 


♦There  are  numerous  incidents  on  record  in  nose  and  throat 
literature  which  indicate  that  when  deflected  nasal  septa  and 
other  obstructive  conditions  of  the  nose  and  throat  have  been 
surgically  removed,  there  has  been  a  coincident  benefit  as  regards 
the  number  and  severity  of  the  epileptic  seizures.  Many  times 
these  obstructions  are  not  altogether  organic,  and  when  the 
mucosal  infiltration  is  associated  with  thyroid  insufficiency  and 
is  removed  by  thyroid  therapy,  the  results  are  equally  good. 


140  THE  INTERNAL  SECRETIONS 

the  menses,  and  epilepsy.  It  is  common  to  find  that 
some  menstrual  irregularity,  or  even  what  appears 
to  be  the  normal  menstruation,  seems  a  signal  for 
the  onset  of  a  seizure.  Hundreds  of  cases  have  been 
seen  in  which  a  decided  ovarian  element  was  pres- 
ent, and,  in  most  of  these,  I  am  sure  that  there  has 
been  an  equally  prominent  thyroid  disturbance 
which  many  times  was  responsible,  in  part  at  least, 
for  the  epileptic  and  the  menstrual  disturbances. 

In  passing,  I  might  mention  an  interesting  and 
somewhat  confirmatory  report  by  Weeks  and  Ren- 
ner  (3)  on  a  case  of  Raynaud's  disease  associated 
with  epilepsy.  Within  the  past  year,  no  less  an 
authority  than  Oliver  T.  Osborne,  (4)  of  Yale,  has 
shown  that  the  several  vasomotor  disorders,  of 
which  Raynaud's  symmetrical  gangrene  is  the  ex- 
treme type  and  chilblains  is  a  lesser  type,  are  al- 
ways associated  with  thyroid  disorder,  although 
other  ductless  glands  may  be  simultaneously  in- 
volved.* According  to  Osborne,  thyroid  therapy, 
judiciously  employed,  causes  improvement  in  most 
cases  of  Raynaud's  disease  and  some  cases  are 
actually  cured. 

There  is  something  more  than  incidental  in  the 
relation  of  the  alimentary  conditions  in  epilepsy  to 


*Let  me  mention  here,  parenthetically,  that  it  is  practically- 
impossible  to  have  a  disorder  of  the  endocrine  glands  involving 
a  single  gland  of  internal  secretion.  Their  hormonic  relation  is 
so  intimate  (or  as  McCord  has  so  well  expressed  it,  the  glands 
of  internal  secretion  constitute  an  "interlocking  directorate  which 
controls  the  body"),  that  uniglandular  disorder  invariably  means 
a  pluriglandular  complex. 


IN  PRACTICAL  MEDICINE  141 

those  we  may  expect  in  chronic  hypothyroidism.  In 
epilepsy  it  has  long  been  recognized  that  the  ten- 
dency to  constipation  invariably  present  (despite 
the  fact  that  we  are  often  told  that  "the  bowels 
move  quite  normally")  complicates  the  disease  by 
aggravating  the  intensity  and  frequency  of  the 
seizures.  It  is  now  universally  known  that  one 
must  always  give  special  care  to  the  bowels,  irre- 
spective of  seeming  normality,  and  also  cut  down 
the  protein  intake,  especially  the  amount  of  meat. 
In  hypothyroidism,  also,  a  similar  form  of  consti- 
pation is  the  rule.  Leopold  Levi,  (5)  the  greatest 
French  authority  on  thyroid  dyscrasias,  lays  em- 
phasis on  his  opinion  that  constipation  of  thyroid 
origin  is  frequent  and,  perhaps,  is  the  most  frequent 
form  of  constipation. 

Both  epilepsy  and  thyroid  disorders  very  com- 
monly have  an  hereditary  predisposition  underly- 
ing them.  Cretinism,  of  course,  is  not  an  acquired 
disease,  and  the  hereditary  tendency  to  thyroid  in- 
stability is  one  of  the  easiest  to  trace  back  of  all  of 
the  factors  present,  I  need  only  remind  you  of  the 
frequency  of  thyroid  instability  in  the  children  of 
parents,  and  especially  mothers,  with  irregularities 
of  the  ductless  glands,  or  mention  the  well-known 
fact  that  an  undue  strain  upon  the  thyroid  appa- 
ratus prior  to  or  during  pregnancy  is  the  most 
usual  basic  cause  for  many  of  the  varying  degrees 
of  thyroid  inadequacy  that  we  discover  almost  ev- 
ery day  if  we  look  keenly  for  them. 


142  THE  INTERNAL  SECRETIONS 

Thorn*  studied  157  cases  of  epilepsy  quite  re- 
cently and  found  that  no  less  than  126  showed  a 
direct  hereditary  connection — either  a  parent  or  a 
grandparent  had  the  disease.  In  thirty-eight  per 
cent,  of  the  series  studied,  epilepsy  was  associated 
with  alcoholism — one  of  the  commonest  causes  of 
acquired  or  transmitted  functional  or  organic  en- 
docrine disorders.  Mental  disorders  were  pres- 
ent in  twenty-seven  per  cent,  of  the  parents  of  these 
cases  and  feeble-mindedness  in  more  than  ten  per 
cent.  We  need  not  more  than  mention  in  passing 
that  one  of  the  most  frequent  causes  of  feeble- 
mindedness is  thyroid  disorder,  and  that  insanity 
has  been  connected  by  numerous  writers  with  dis- 
orders of  one  or  more  of  the  ductless  glands,  usu- 
ally the  thyroid  or  the  ovaries,  as  often  as  with  any 
single  condition.  Still  further,  I  am  confident  that 
some  dav  it  will  be  better  understood  that  the  two 
most  prolific  causes  of  insanity — syphilis  and  alco- 
holism— bring  it  about  by  their  insidious  disorgan- 
ization of  the  work  of  the  glands  of  internal  secre- 
tion, more  than  in  any  other  manner. 

There  are  various  communications  in  the  French 
medical  literature,  to  which  reference  should  be 
made.  Gauthier  (6)  has  collated  many,  and  sup- 
plements them  with  several  personal  case  reports. 
He  finds  that  thyroid  therapy  is  a  helpful  measure 
in  epilepsy,  especially  where  other  evidences  of  thy- 


*  Figures   quoted    from   editorial    in   Ellingwood's   Therapeu- 
tist, 103   (1916). 


IN  PRACTICAL  MEDICINE  143 

roid  insufficiency  are  present.  It  may  be  well  to 
translate  a  few  lines  from  his  book : 

''Epilepsy  is  considered  by  a  large  number  of 
physicians  and  neurologists  to  be  an  intoxication., 
or  a  general  disorder  of  metabolism.  There  is  also 
a  possible  connection  in  certain  cases  with  the  work 
of  the  thyro-parathyroid  combination.  The  asso- 
ciation of  epilepsy  with  myxedematous  idiocy, 
cretinism  and  even  Basedow's  disease  is  well 
known.  But  there  are  other  evidences.  Many  cases 
of  simple  goiter  become  epileptic  and  goiterous 
mothers  give  birth  to  epileptic  children  (Rapp, 
Jeandelize,  Parhon,  Goldstein,  Hertoghe,  etc.). 
Claude  and  Schmiergeld,  (7)  in  a  study  of  seven- 
teen cases  of  epilepsy  from  the  endocrine  point  of 
view,  have  found  in  every  case  alterations  in  the 
thyroid  gland  and  in  twelve  of  these  the  structure 
of  the  gland  was  completely  altered  with  areas  of 
sclerosis  and  limited  zones  of  compensatory  hyper- 
trophy of  the  glandular  tissue.  .  .  .  Parhon  (8) 
examined  the  thyroid  in  twelve  epileptics.  He 
found  it  smaller  than  usual  and  showing  frequent 
and  variable  histologic  changes,  and,  interestingly 
enough,  the  iodin  content  was  very  often  in- 
creased." 

The  cerebral  edema  which  Reed  and  Martin 
Fischer  of  Cincinnati  are  now  convinced  is  a  result 
of  the  toxic  acidosis,  is  just  as  likely  to  be  of  thy- 
roid as  of  intestinal  origin,  for  not  only  may  the 
acidosis  or  systemic  hypoalkalinity  result  from  the 


144  THE  INTERNAL  SECRETIONS 

loss  of  the  full  effective  hormonic  service  of  the  thy- 
roid, but  the  essential  infiltration,*  which  is  the 
typical  pathognomonic  feature  of  hypothyroidism 
affects  all  the  tissues  of  the  body,  for  the  thyroid 
exerts  a  cellular  influence  which  is  not  limited  to 
any  organ  or  set  of  organs,  hence,  not  only  the 
brain,  but  also  the  peritoneal  and  mesenteric  glands 
may  be  infiltrated  as  noted  by  Reed  and  mentioned 
in  the  beginning  of  this  paper.  In  this  connection 
it  may  be  well  to  state  that  Hertoghe  (9)  has  de- 
scribed a  form  of  coma  of  thyroid  origin  in  which 
one  of  the  constant  findings  on  autopsy  was  an  in- 
filtrative edema  of  the  brain. 

A  certain  well-defined  fact,  first  set  forth  by  Her- 
toghe and  later  by  Leopold  Levi,  enables  us  to  give 
a  final  emphatic  demonstration  that  the  position 
held  regarding  the  importance  of  the  thyroid  ele- 
ment in  epilepsy  is  not  untenable.  Benefit  from 
thyroid  therapy  can  not  be  expected  in  the  numer- 
ous conditions  for  which  it  is  given  unless  there  is 
a  definite  need  for  the  chemical  substances  or  hor- 


*The  most  marked  result  of  the  loss  of  the  thyroid  hormone 
is  a  condition  of  cellular  inactivity  and  mal-elimination.  This 
results  in  a  peculiar  form  of  infiltration  which  may  affect  any 
cells  that  are  under  the  influence  of  this  gland.  This  means 
practically  all  forms  of  tissue.  This  infiltration  is  hest  recog- 
nized in  the  puffy,  dough-like  skin  of  myxedema,  and  while  it 
may  not  be  so  marked,  it  is  the  principal  cause  of  the  majority 
of  the  manifestations  of  thyroid  insufficiency.  One  can  readily 
understand  that  the  obesity,  stiffness  of  the  muscles,  ligaments 
and  joints,  intestinal  sluggishness,  and  in  fact,  disturbed  cell 
activities  in  general,  including  the  brain,  nerves  and  tissues  gen- 
erally, may  be  thus  referred  to  a  more  or  less  well-marked 
metabolic  inactivity  which  follows  the  loss  of  the  essential  hor- 
mone stimuli  which  the  thyroid  sends  to  every  part  of  the  body. 


IN  PRACTICAL  MEDICINE  145 

mones  thus  administered.  In  Levi's  words  (10): 
"When  the  results  of  treatment  with  thyroid  ex- 
tract are  immediate,  continued,  constant  or  pro- 
nounced, they  may  be  regarded  as  a  diagnostic  fac- 
tor." Hertoghe  tells  us  the  same  thing  in  other 
words:  "If  certain  patients  are  carefully  exam- 
ined, they  will  be  found  to  show  symptoms  of  gen- 
eral thyroid  insufficiency,  and  this  is  invariably  the 
case  with  those  who  derive  benefit  from  thyroid 
medication." 

There  are  not  a  few  reports  from  which  we  may 
gather  that  empirical  thyroid  therapy  has  exerted 
some  beneficial  effect  in  epilepsy.  I  have  noticed 
this  a  number  of  times  myself,  though  I  should  not 
want  to  imply  that  the  benefit  was  solely  due  to 
the  thyroid  medication.  Many  of  us,  perhaps,  have 
given  this  remedy  in  anticipation  of  a  possible  bene- 
fit just  as  we  have  come  to  expect,  somewhat  un- 
scientifically it  is  true,  that  thyroid  extract  may 
help  a  host  of  widely  differing  conditions.  These 
scattered  results  are  among  the  best  reasons  for  ap- 
plying the  etiologic,  diagnostic  and  therapeutic 
principle  which  I  am  discussing.  When  applied 
systematically  in  the  routine  treatment  of  epilepsy 
in  which  one  can  find  clinical  evidence  of  hypothy- 
roidism, accompanied,  of  course,  with  such  other 
curative  and  symptomatic  treatment  as  the  exi- 
gencies of  each  case  demands,  the  prognostic  pros- 
pects should  be  considerably  better. 

With  these  opinions  in  mind,  we  are  justified  in 


146  THE  INTERNAL  SECRETIONS 

drawing  some  conclusions  which  seem  to  have  a 
reasonable  bearing  on  the  subject  under  discussion: 

1.  That  thyroid  insufficiency  is  likely  to  be  a  fre- 
quent underlying  factor  in  the  etiology  of  epilepsy 
for  several  reasons:  (a)  It  favors  toxemia;  (b)  it 
produces  cellular  infiltration  and  edema,  which  may 
affect  the  brain  in  the  manner  described  by  Her- 
toghe,  Reed  and  others,  and  (c)  it  usually  causes 
other  symptoms  in  epilepsy  which  have  been  defi- 
nitely attributed  to  hypothyroidism. 

2.  Hence  the  study  of  epilepsy  from  the  stand- 
point of  the  glands  of  internal  secretion  is  rational 
and  worth  while. 

3.  Thyroid  therapy  is  a  rational  therapeutic  ad- 
junct in  the  treatment  of  epilepsy  accompanied  by 
other  signs  of  hypothyroidism. 

4.  Favorable  results  from  the  use  of  thyroid  ex- 
tract in  epilepsy  should  be  considered  as  a  confirma- 
tion of  these  conclusions;  and  an  incentive  to  fur- 
ther clinical  study  in  this  direction. 

In  closing  I  do  not  want  to  leave  the  impression 
that  a  few  weeks  of  thyroid  therapy  will  cure  epi- 
lepsy. Rather  do  I  wish  to  emphasize  that  the  thy- 
roid gland,  because  of  its  intimacy  with  detoxica- 
tion  and  metabolism  in  general,  deserves  to  be  con- 
sidered in  the  investigation  of  every  case  of  epi- 
lepsy; and  where  one  finds  other  evidences  of 
waning  thyroid  sufficiency,  thyroid  therapy  may  be 
instituted  in  conjunction  with  other  rational  treat- 
ment, and  a  better  percentage  of  results  be  attained. 


IN  PRACTICAL  MEDICINE  147 

REFERENCES 

1.  C.  A.  L.  Reed:  Journal  Am.  Med.  Assn.,  66,  336 
(1916) ;  Journal  Am.  Med.  Assn.,  64,  1,047  (1915)  ;  Lancet- 
Clinic,  112,  102  (1914). 

2.  E.  Hertoghe:     Practitioner,  94,  24  (1915). 

3.  D.  F.  Weeks  and  D.  S.  Renner:  Jour.  Am.  Med. 
Assn.,  66,  651  (1916). 

4.  O.  T.  Osborne:  Am.  Jour.  Med.  Sci.,  150,  157 
(1915)  ;  see  also  Amer.  Med.,  10,  784  (1915). 

5.  L.  Levi :  "La  Petite  Insuffisance  Thyroidienne  et 
son  Traitement,"  Paris,  1913,  p.  91. 

6.  G.  Gauthier:  "L'Opotherapie  Thyroidienne,"  358. 
Paris,  1913. 

7.  H.  Claude  and  Schmiergeld :  Les  Glandes  a  Secre- 
tions Internes  chez  les  Epileptiques,  L'Encephale,  Janu- 
ary, 1909. 

8.  Parhon  et  al :    Rev.  Neurologique,  January,  1908. 

9.  E.  Hertoghe :  Du  Coma  Myxedemateux.  Bull 
Acad.  Roy.  de  Med.  de  Belg.,  February  25,  1911. 

10.  Leopold  Levi:     Practitioner,  94,  199,  1915. 


XIII 

THE  DEFECTIVE  CHILD  FROM  THE 

STANDPOINT  OF  THE  INTERNAL 

SECRETIONS 

DEFECTIVE  children,  or  "children  requiring" 
special  attention"  as  a  colleague  appreciative  of  the 
sensibilities  of  the  parents  calls  them,  are  practic- 
ally without  exception  endocrine  cases. 

There  are  several  comprehensive  classifications 
of  defectives;  and  the  methods  of  measuring  their 
physical  and  mental  capacity,  or  lack  of  it,  enables 
us  to  place  a  given  case  in  the  same  class  as  others 
affected  in  a  similar  degree.  This,  however,  does 
not  indicate  the  etiologic  factors  influencing  the 
child  and,  hence,  the  proper  treatment. 

It  is  true  that  children  handicapped  with  hered- 
itary syphilis,  epilepsy  or  any  transmitted  disease 
or  disease  tendency,  more  often  are  considered  as 
syphilitic  or  epileptic  rather  than  as  suffering  from 
dyscrinism.  Nevertheless  the  fact  remains  that  in 
all  such  cases  the  endocrine  element  is  both  pres- 
ent and  prominent  irrespective  of  the  simplicity  or 
complexity  of  the  trouble  and  its  cause. 

With  our  present  knowledge  we  may  safely  say 
that  the  treatment  of  defective  children  offers  bet- 
ter prospects  of  success  than  ever  before.  Of  course 


Reprinted   from  the   Southern   California   Practitioner    (Los 
Angeles)   July,  1917. 

(148) 


IN  PRACTICAL  MEDICINE  149 

what  is  known  as  feeble-mindedness  or  amentia 
may  be  more  than  a  mere  "deficiency,"  for  the  cere- 
bral development  may  be  imperfect  and  here  there 
is  little  or  no  hope  for  a  successful  outcome. 

In  the  past  few  years  considerable  interest  has 
been  aroused  in  the  relation  of  endocrinology  and 
the  study  of  defective  children;  and  it  is  surprising 
how  many  of  the  stigmata  which  cause  us  to  place 
children  in  this  category  are  connected  with  abnor- 
mal endocrine  function  and,  too,  how  frequently  on 
investigating  their  antecedents  we  uncover  a  more 
or  less  well  marked  endocrine  disorder  in  the 
parents  or  grandparents  which  properly  may  be  re- 
garded as  a  part  of  the  cause  of  these  unfortunate 
conditions  in  their  offspring. 

The  hereditary  phase  of  the  relation  of  dyscrin- 
ism  to  defectives  will  be  referred  to  again  later  as 
it  seems  to  be  a  hopeful  phase  of  a  very  hopeless 
subject. 

It  will  be  my  endeavor  here  to  lend  emphasis  to 
the  importance  of  considering  this  subject  from 
the  chemical  rather  than  the  physical  standpoint, 
and  to  secure  more  attention  by  readers  to  the 
study  of  the  ductless  glandular  manifestations,  ob- 
vious or  insidious,  in  defective  children. 

There  are  almost  as  many  forms  of  develop- 
mental anomalies  in  children  as  there  are  glands  of 
internal  secretion.  Chief  among  them  all  are  those 
relating  to  dysthyroidism.  The  cretin,  well  known 
to  be  typical  of  a  large  class  of  deficients,  is  an 


150  THE  INTERNAL  SECRETIONS 

endocrine  case  pure  and  simple,  the  syndrome  be- 
ing definitely  traced  to  deficient  thyroid  activity 
and,  fortunately,  being  decidedly  benefited  by  sub- 
stitution therapy  or  the  administration  of  the  miss- 
ing chemical  substances.  In  fact  a  large  part  of 
our  first  knowledge  of  the  clinical  importance  of 
dysthyroidism  resulted  from  the  studies  of  George 
Murray,  Sir  William  Gull  and  Theodore  Kocher 
some  twenty-five  years  ago  upon  individuals  who 
were  all  in  one  way  or  another  mentally  and  phys- 
ically defective. 

The  literature  upon  the  retarded,  backward  or 
deficient  child  recently  has  begun  to  contain  ref- 
erences to  the  syndrome  "hypoplasia"  and  accord- 
ing to  Noble  (1)  the  hypoplastic  individual  is  one 
whose  nutrition  and  development  is  below  par,  the 
condition  being  congenital  or  acquired  during  in- 
fancy or  early  childhood.  There  are  varying  de- 
grees of  hypoplasia  reaching  from  backwardness 
which  is  not  appreciated  until  the  child  has  been 
some  time  in  school,  to  the  serious  organic  dyscrin- 
ism  which  is  sometimes  called  infantilism  and 
sometimes  mal-development. 

It  is  difficult  to  say  how  much  of  the  symptom- 
atology of  this  condition  of  hypoplasia  may  be  re- 
ferred to  the  thyroid  gland.  Much  of  it  at  least 
is  of  thyroid  origin  and  Hertoghe  (2)  refers  to  it 
frequently  in  his  writings  and  uses  the  term  "thy- 
roid inanition"  as  indicating  a  condition  of  slow 
starvation  and  inactivity  without  particularly  ob- 


IN  PRACTICAL  MEDICINE  151 

vious  changes  in  contour  or  weight.  Function, 
however,  is  much  below  par  and  it  is  but  a  short 
step  from  the  unappreciated  "forme  fruste"  of  thy- 
roid insufficiency  to  the  myxedematous  idiocy  de- 
scribed by  Brissaud,  or  the  Lorain  type  of  infantil- 
ism, in  the  former  of  which  mental  development 
seems  to  be  more  definitely  affected  while  in  the 
latter  the  mind  is  clear  and  capable  and  physical 
development  is  deficient. 

Hypoplasia  in  children  according  to  E.  B.  Mc- 
Cready  of  Pittsburgh,  who  is  a  close  and  intelligent 
student  of  this  subject,  properly  may  include  the 
backward  child  "who  is  retarded  in  his  develop- 
ment by  reason  of  some  condition  either  inherent 
in  the  child  himself,  which  can  either  be  removed 
or  counteracted,  or  who  is  subject  to  some  physical 
defect  or  environmental  condition,  the  removal  of 
which  will  allow  him  to  progress  in  a  normal  man- 
ner under  favorable  opportunities."  (3) 

From  the  standpoint  of  this  author,  with  whom 
I  am  heartily  in  accord,  the  hypoplastic  child  is  not 
necessarily  a  sufferer  from  an  unchangeable  de- 
velopmental complex.  The  stimuli  to  growth  and 
development  have  not  been  sufficiently  strong  and 
these  necessary  manifestations  are  at  a  standstill 
or  below  par.  Fortunately  this  class  constitutes  a 
large  proportion  of  the  so-called  "backward  chil- 
dren" and  from  a  clinical  standpoint  the  prognosis 
has  been  radically  changed  for  the  better  since  the 
advent  of  scientific  endocrinology  and  a  better  ap- 


152  THE  INTERNAL  SECRETIONS 

preciation  of  the  possibilities  of  substitution  ther- 
apy. 

The  hypoplastic  individual  is  suffering  from  an 
arrested  development.  All  function  is  at  half-speed 
or  even  slower  and  among  the  early  symptoms 
enumerated  by  McCready  (4)  are :  Delay  in  the 
power  of  walking  and  talking,  late  closing  of  the 
fontanelles,  irregular  dentition,  though  progress 
in  these  respects  may  be  entirely  normal  and  even 
more  rapid  than  normal  for  the  precocious  child 
is  often  an  hypoplastic  one.  Additional  early  signs 
are  nocturnal  enuresis,  the  so-called  scaphoid  scap- 
ula, a  tendency  to  lymphatism  with  adenoids  and 
hypertrophied  tonsils,  and  pronounced  malnutri- 
tion. 

Leonard  Williams  (5)  has  brought  together 
enough  clinical  and  therapeutic  evidence  to  estab- 
lish the  fact  that  enuresis  in  the  hypoplastic  child 
is  largely  a  result  of  thyroid  insufficiency,  which  is 
so  commonly  present,  and  the  successful  admin- 
istration of  thyroid  extract  in  these  cases  tends  to 
bear  out  this  contention.  Incidentally  Williams 
believes  that  adenoids  and  enlarged  tonsils  repre- 
sent a  compensatory  action  of  the  body,  tending 
to  counterbalance  the  thyroid  insufficiency. 

Graves  (6)  finds  the  scaphoid  scapula  so  com- 
mon in  these  cases  that  in  a  report  of  47  children 
who  were  behind  in  their  grades,  all  were  under 
size  and  showed  various  anomalies  in  development, 
58  per  cent,  were  mouth  breathers,   17  per  cent. 


IN  PRACTICAL  MEDICINE  153 

were  subject  to  enuresis  and  85  per  cent,  showed 
the  scaphoid  scapula.  Another  fairly  constant 
symptom,  according  to  McCready,  is  the  high- 
arched  palate  which  is  presumed  to  be  produced  by 
the  yielding  of  the  palatine  bones  owing  to  their 
relative  deficiency  in  calcium.  Enlarged  tonsils 
and  adenoids,  while  common  enough,  are  more 
likely  to  occur  in  hypoplastic  children  and  accord- 
ing to  Noble  (1)  this  pathological  condition  of  cell 
hypoplasia  explains  the  reason  for  a  large  group 
of  debilitated  women  and  also  all  the  children  who 
are  not  vigorous  and  who  have  adenoids  and  dis- 
eased tonsils  and  who  become  mouth  breathers. 

It  is  not  possible  within  the  limits  of  this  brief 
communication  to  mention  a  tithe  of  the  state- 
ments in  the  last  ten  or  fifteen  years  regarding  the 
endocrine  basis  of  developmental  disorders  in  chil- 
dren, but  if  the  students  of  these  "children  requir- 
ing special  attention"  will  look  carefully  for  the 
functional  accompaniments  of  thyroid  insuffi- 
ciency* (7)  they  will  be  found  in  a  large  proportion 
of  the  cases. 

Probably  the  next  most  important  gland  that 
deserves  study  in  this  class  of  cases  is  the  thymus, 
for  thymus  enlargement  or  in  older  children  the 
persistent  thymus,  is  found  to  be  very  com- 
monly connected  with  disorders  of  this  character, 


*To  avoid  repetition  the  reader  is  asked  to  read  Chapter  IV 
in  this  connection  and  especially  the  symptomatology  of  hypo- 
thyroidism as  outlined  on  page  38. 


154  THE  INTERNAL  SECRETIONS 

just  as  a  premature  atrophy  or  absence  of  the  thy- 
mus also  may  be  found.  Hard  and  fast  statements 
can  not  yet  be  made  as  to  the  real  function  of  this 
gland.  Some  deny  its  internal  secretory  powers 
and  call  it  merely  lymphoid  tissue.  Not  all  are 
unanimous  about  the  relations  of  this  gland,  but 
from  a  clinical  standpoint,  I  am  certain  that  the 
thymus  is  involved  in  many  cases  of  this  character 
for  I  have  personally  demonstrated  an  enlarged 
thymus  in  a  number  of  children  that  have  come  to 
me  for  diagnosis  or  treatment  and  following  a  flu- 
oroscopic examination  I  have  had  these  children 
irradiated  and  later  on  re-examination  have  dis- 
covered a  considerable  reduction  in  the  thymic 
shadow  which  was  accompanied  by  benefit  to  the 
symptom  complex  under  treatment  (though  of 
course  I  admit  that  this  procedure  just  mentioned 
was  but  a  part  of  the  treatment). 

There  is  no  question  about  the  defectiveness  of 
children  suffering  from  the  well-defined  status 
thymicolymphaticus,  though  mentality  may  be 
normal.  In  such  cases  an  early  diagnosis  may  be 
facilitated  by  a  differential  blood  count  in  which 
the  lymphocytes  will  be  found  to  be  greatly  in- 
creased (100  per  cent,  or  more).  There  will  be 
hyperplasia  of  various  groups  of  lymph  glands  as 
well  as  the  tonsils  and  spleen  and  the  skin  will  have 
a  pale,  badly  nourished  appearance  and  occasion- 
ally there  will  be  an  associated  mal-development 
of  the  genitalia. 


IN  PRACTICAL  MEDICINE  155 

Thymus  hyperplasia  in  children  is  usually  ac- 
companied by  the  "hypoplastic  state"  referred  to 
before.  The  increased  cellular  growth  of  the  thy 
mus  and  other  lymph  structures  is  modifying  the 
chemistry  of  the  body  in  such  a  way  that  the  defi- 
ciencies of  hypoplasia  are  permitted  to  show  them- 
selves. These  individuals  are  of  the  flabby,  semi- 
obese  type  and  practically  always  have  other  evi- 
dences of  developmental  dystrophy.  Occasionally 
in  addition  to  the  osseous  changes  already  men- 
tioned (high  arched  palate  and  scaphoid  scapula) 
the  bony  development  is  modified  seriously,  the 
epiphyses  are  late  in  joining  and  rickets  may  be 
present.* 

On  the  other  hand,  Bourneville  has  shown  from 
a  large  series  of  autopsy  findings  that  over  70  per 
cent,  of  mentally  defective  and  epileptic  children 
have  no  thymus  at  all.  This  may  seem  to  be  contra- 
dictory but  it  is  none  the  less  suggestive  as  it  di- 
rects attention  to  the  thymus  as  a  regulator  of  the 
chemistry,  and  whether  deficient  or  excessively 
active,  it  is  a  factor  deserving  of  our  study. 

While  it  is  granted  that  our  knowledge  of  the 
thymus  gland  is  none  too  definite  as  yet,  we  are 
safe  in  assuming  it  to  be  an  important  factor  in 
defective  children,  and  initiating  a  careful  physical 
examination  for  the  gland  itself  and  a  search  for 

*A  number  of  writers  indicate  a  clinical  connection  between 
thymus  disorder  and  rickets;  and  the  subject  is  considered  from 
the  standpoint  of  treatment  in  the  prize  article  which  consti- 
tutes Chapter  XVIII. 


156  THE  INTERNAL  SECRETIONS 

evidences  of  dysthymism.  If  this  search  is  unre- 
munerative  it  is  a  great  advantage  to  me  to  have 
ruled  out  the  likelihood  of  thymic  involvement  for 
not  infrequently  it  is  present  and  ignored  alto- 
gether with  obvious  detriment  to  the  success  of  the 
best  of  treatment. 

Still  another  gland  is  prominently  identified  with 
developmental  disorders  in  children.  The  hypo- 
physis or  pituitary  has  much  to  do  with  the  chem- 
ical control  of  development  and  while  it  may  not 
be  so  important  as  the  thyroid  it  is  more  important 
than  some  have  thought.  Quite  the  most  important 
recent  step  in  the  development  of  our  knowledge 
of  the  ductless  glands  is  the  discovery  by  T.  Brails- 
ford  Robertson  of  the  University  of  California  of 
the  active  principle  of  the  pituitary  gland  proper, 
tethelin,  and  its  growth-controlling  function.  (8) 
It  is  entirely  possible  that  in  tethelin  we  may  find 
a  most  useful  means  of  stimulating  deficient 
growth  though  to  date  the  use  of  this  principle  has 
been  largely  limited  to  the  laboratory.  So  far  I 
have  used  the  desiccated  anterior  lobe  of  the  pitu- 
itary in  fourteen  cases  with  advantage  in  enough 
to  establish  my  confidence  in  this  form  of  treat- 
ment. Suffice  it  to  say  that  many  deficiencies  in 
children  have  a  pronounced  pituitary  origin  and  it 
is  a  routine  in  my  work  to  study  all  such  children 
from  a  pituitary  standpoint.  Radiographs  of  the 
sella  turcica  are  made,  and  quite  often  I  have  found 
obvious  changes  in  the  shape  and  size  of  the  pitu- 


IN  PRACTICAL  MEDICINE  157 

itary  fossa.  An  interesting  case  is  already  men- 
tioned elsewhere  in  this  book*  and  while  pituitary 
feeding  is  being  practiced  more  frequently,  too 
often  I  am  finding  that  this  has  been  done  in  cases 
coming  to  me  for  consultation,  without  any  ac- 
curate reason  therefor  and  naturally  without  good 
results.  I  have  in  mind  a  case  of  developmental 
dystrophy  that  had  been  treated  for  many  months 
first  with  thyroid  and  then  with  pituitary  and  then 
with  both,  without  the  slightest  beneficial  results. 
The  case  was  none  the  less  one  in  which  gland 
feeding  was  in  order,  but  this  was  not  successful 
until  given  with  reason  and  accompanied  by  such 
adjuvant  procedures  as  needed  to  be  carried  out 
simultaneously.  In  other  words,  it  is  bad  policy 
to  treat  symptoms  instead  of  patients,  for  not  in- 
frequently such  treatment  is  unsuccessful  and  the 
interest  of  physician  and  parent  in  this  is  lost  when 
in  reality  it  is  the  only  hopeful  thing. 

Pituitary  infantilism  is  very  completely  studied 
and  illustrated  by  Cushing  and  his  monograph*  is 
the  most  comprehensive  piece  of  literature  on  the 
subject  extant. 

The  adrenals  likewise  may  be  involved  and  ad- 
renal sensitiveness  is  not  uncommon  in  defective 
children.  Slight  psychic  or -emotional  stimuli  make 
a  very  great  impression  on  them.     They  fatigue 


*See  Chapter  V,  page  58. 

*The  Pituitary  Body  and  Its  Disorders,  by  Harvey  Cushing, 
J.   B.   Lippincott   Co.,    1912,   Philadelphia. 


158  THE  INTERNAL  SECRETIONS 

easily  and  the  cardiovascular  tone  is  low.  I  have 
noted  a  number  of  times  a  peculiar  bluish  mottling 
of  the  skin,  especially  of  the  lower  parts  of  the 
body  and  a  tendency  to  dermographia,  which  I 
have  laid  to  some  adrenal  element  in  the  pluri- 
glandular disturbance.  These  circulatory-cutane- 
ous manifestations  may  not  be  of  great  diagnostic 
significance  per  se,  but  they  are  of  value  as  indi- 
cators of  a  prospective  dyscrinism  and  a  means  of 
stimulating  further  study  of  the  endocrine  func- 
tions. 

Already  considerable  emphasis  has  been  laid 
upon  the  importance  of  pluriglandular  dystrophies 
and  I  may  say  that  I  have  never  seen  a  defective 
child  in  which  there  was  a  pure  monoglandular 
disorder,  and  I  do  not  believe  there  ever  has  been 
such  a  case.  The  reasons  for  this  have  already  been 
quite  fully  discussed  elsewhere  in  this  book  and  the 
obvious  therapeutic  indication  is  to  be  sure  that 
our  treatment  is  comprehensive. 

McCready*  in  his  work  along  this  line  has  de- 
vised a  combination  of  glandular  extracts  which 
he  has  had  prepared  for  him  by  Messrs.  Burroughs, 


*I  think  it  is  only  proper  to  give  much  credit  to  Dr.  Mc- 
Cready  for  the  aggressive  and  intensive  way  in  which  he  has 
studied  what  he  chooses  to  call  "pedology."  He  has  unusual 
facilities  in  the  Children's  Courts  at  Pittsburgh  and  also  his 
institution  "Wildwood  Hall"  offers  ideal  facilities  for  the  suit- 
able care  of  children  requiring  special  attention.  The  success- 
ful treatment  of  this  class  of  cases  involves  not  merely  glandu- 
lar feeding  but  intimate  hygienic  and  dietetic  control,  special 
education  and  an  ideal  environment;  and  it  is  almost  impossible 
to  secure  these  at  home  or  in  most  institutions  in  which  such 
cases  are  handled  by  the  State. 


IN  PRACTICAL  MEDICINE  159 

Wellcome  &  Co.  This  is  now  obtainable  in  trade 
under  the  name  "Tabloid  Mixed  Glands"  and  to 
my  mind  this  is  a  much  more  satisfactory  treat- 
ment than  the  single  extracts  which  we  have  been 
wont  to  use  in  the  past,  and  it  has  the  advantage 
of  enabling  one  to  stimulate  the  endocrine  system 
as  a  whole  rather  than  a  part  of  it;  and  where 
necessary,  by  adding  additional  amounts  of  such 
other  extracts  as  may  seem  to  be  indicated,  spe- 
cial homo-stimulation  may  be  brought  about. 

It  would  not  be  proper  to  dismiss  the  subject 
without  considering  a  phase  of  it  which  is  deserv- 
ing of  much  more  concerted  study  and  action.  Not 
a  little  concentrated  attention  has  been  directed  at 
the  huge  task  before  the  medical  profession  of  pre- 
venting as  far  as  possible  the  dire  results  of  mental 
and  physical  defects  and  diminishing  the  extent  of 
this  most  pitiful  of  all  phases  of  social  medicine. 

Perhaps  the  most  reasonable  and  practically  in- 
teresting communication  on  this  subject  is  the  ad- 
dress by  Sajous  (9)  in  which  he  makes  a  plea  for 
co-operation  along  a  line  which  is  altogether  new. 
Sajous  brings  sufficient  evidence  to  show  that 
glandular  insufficiencies  of  a  minor  character  in 
mothers  are  likely  to  be  impressed  upon  their  un- 
born offspring  and  the  obvious  thing  to  do  in  cases 
of  this  character  is  to  be  sure  that  these  insuffi- 
ciencies are  minimized  at  the  time  when  this  treat- 
ment will  offer  the  greatest  prospects  of  results.  In 
other  words,  if  a  mother  is  suffering  from  thyroid 


160  THE  INTERNAL  SECRETIONS 

insufficiency  it  is  likely  that  her  child  will  have 
leanings  in  the  same  direction  and  thyroid  feeding 
is  in  order  during  pregnancy.  I  have  personally 
discovered  in  scores  of  cases  a  very  clear  relation 
between  ductless  glandular  disturbances  in  the 
mother  and  her  offspring.  In  fact  it  is  almost  the 
rule  to  find  that  the  woman  with  a  goiter  transmits 
a  tendency  to  goiter  to  her  daughter  and  when  pa- 
tients come  for  treatment  the  history  will  show 
almost  always  a  hereditary  basis  for  troubles  of 
this  character. 

I  can  do  no  better  than  to  select  a  few  weighty 
sentences  from  Doctor  Sajous'  address,  as  by  re- 
printing them  a  greater  appreciation  of  this  sub- 
ject may  be  stimulated: 

"Any  disease  capable  of  injuring  the  ductless 
glands  sufficiently  to  inhibit  their  functional  activ- 
ity impairs  correspondingly  the  development  and 
functional  activity  of  the  brain,  by  reducing  the 
supply  of  secretions  this  organ  requires  to  carry 
on  these  physiological  processes." 

"The  main  underlying  cause  of  defective  men- 
tality in  both  parent  and  offspring  is  inherited  de- 
ficient activity  of  the  ductless  glands." 

"We  should  start  a  campaign  having  in  view  the 
salvation  of  these  unfortunate  infants  by  supply- 
ing, through  the  intermediary  of  their  defective 
mothers,  and,  after  birth,  through  their  food,  the 
secretions  they  lack  to  complete  their  develop- 
ment." 


IN  PRACTICAL  MEDICINE  161 

"In  the  majority  of  functional  cases  of  feeble- 
minded and  backward  children  met  in  current 
practice,  the  predominating  pathogenic  factor  is 
hypothyroidism,  though  deficiency  of  other  inter- 
nal secretions  is  also  discernible  in  most  instances." 

"On  the  whole,  the  intimate  relationship  between 
the  ductless  glands  and  everything  that  concerns 
reproduction,  the  greater  relative  size  of  these  or- 
gans in  the  product  of  conception,  and  the  teach- 
ings of  practical  experience  in  organotherapy,  all 
tend  to  indicate  that  whenever  the  father  or  mother 
is  a  mental  defective,  or  both  parents  show  any 
sign  of  deficient  activity  of  one  or  more  ductless 
glands,  or  are  mental  defectives,  organotherapy 
should  be  instituted  as  soon  as  pregnancy  is  recog- 
nized." 

"The  mental  and  physical  status  of  all  pregnant 
women  as  regards  the  functional  efficiency  of  their 
ductless  glands,  which  may  be  determined  by  the 
stigmata  of  deficiency  of  these  organs,  should  in- 
variably be  established.  If  found  deficient,  organo- 
therapy should  be  used  to  protect  them  against 
renal  disorders  and  convulsions  through  toxemia, 
and  also  their  offspring  against  imperfect  develop- 
ment and  mental  deficiency." 

In  closing  I  feel  to  add  that  the  foregoing  state- 
ments are  deserving  of  the  closest  attention,  and 
that  the  principle  so  clearly  enunciated  applies  to 
all  deficients  or  defectives  and  not  merely  to  those 
in  which  the  mental  element  predominates. 


162  THE  INTERNAL  SECRETIONS 

REFERENCES 

1.  Chas.  P.  Noble,  Hereditary  Hypoplasia  in  Man, 
Due  to  Degeneracy.    Jour.  A.  M.  A.,  Feb.  3,  1909. 

2.  E.  Hertoghe,  Thyroid  Insufficiency.  Practitioner 
(Lond.),  Jan.,  1915. 

3.  E.  Bosworth  McCready,  The  Care  of  the  Excep- 
tional Child.     Arch.  Pediatrics  (N.  Y.),  June,  1911. 

4.  Ibid,  Retarded  Mental  Development  in  Children, 
Internat.  Clin.  (Phila.),  1913,  Vol.  I. 

5.  Leonard  Williams,  Clinical  Lecture  before  Medi- 
cal Graduate  College,  London.  Polyclinic  (Lon.),  Jan.,  1909. 

6.  W.  W.  Graves,  The  Scaphoid  Scapula,  Medical 
Record  (N.  Y.),  May  21,  1910. 

7.  Henry  R.  Harrower,  The  Inconspicuous,  Every- 
day Forms  of  Thyroid  Insufficiency.  California  State 
Journal  of  Medicine  (San  Francisco),  May,  1916. 

8.  T.  Brailsford  Robertson,  Recent  Investigations  of 
the  Influence  of  the  Anterior  Lobe  of  the  Pituitary  Body, 
and  on  the  Properties  of  the  Growth-Controlling  Constitu- 
ent Tethelin.     Endocrinology  (Los  Angeles),  Jan.,  1917. 

9.  Chas.  E.  deM.  Sajous,  Our  Duty  to  Mental  De- 
fectives of  the  Present  Generation.  New  York  Med.  Jour., 
April  1,  1916. 


XIV 

ORGANOTHERAPY  IN  CHRONIC  DISEASE 

WITH  SPECIAL  REFERENCE  TO  ITS 

POSSIBILITIES  IN  CANCER 

THE  treatment  of  chronic  disease,  at  best  too 
often  a  difficult  and  unsatisfactory  matter,  has 
been  considered  by  so  many  physicians  so  many 
times  that  further  reference  to  the  subject  may 
seem  to  be  almost  out  of  place,  for  already  there 
is  an  overwhelming  number  of  papers  and  many 
books  concerned  with  the  advantages  of  all  forms 
of  treatment  of  chronic  disease,  from  the  surgical 
removal  of  presumably  offending  organs  to  the 
Emanuel  Movement,  and  including  other  more  or 
less  useful  methods  such  as  hydrotherapy,  electro- 
therapy, psychotherapy,  serotherapy,  autotherapy, 
and,  most  recent  of  all,  the  intestinal  short  circuit 
as  suggested  by  Sir  Arbuthnot  Lane. 

The  mere  fact  that  disease  has  been  present  for 
more  than  the  proverbial  forty  days  and  that  a 
good  percentage  of  chronic  invalids  perambulate 
from  one  doctor's  office  to  another,  as  well  as  the 
suggestion  already  made  that  many  widely  differ- 
ing forms  of  treatment  are  advanced  more  or  less 
enthusiastically  from  time~to  time,  seem  to  be  con- 


An  address  read  by  invitation  before  the  Medical  Associa- 
tion of  the  Greater  City  of  New  York,  February  15,  1915,  and 
published  in  the  New  York  Medical  Record  July  3,  1915.  (Copy- 
right, William  Wood  &  Company.) 

(163) 


164  THE  INTERNAL  SECRETIONS 

vincing  evidence  that  the  treatment  of  chronic  dis- 
ease is  still  an  unsolved  problem  and  hence  worthy 
of  persistent  study. 

This  evening  it  is  proposed  to  consider  another 
fairly  well  known  phase  of  therapeutics  and  to  urge 
its  more  frequent  application  to  the  indefinite  and 
chronic  disorders,  many  of  which  have  not  the 
dignity  of  a  name  and  others  of  which  are  classed, 
rightly  or  wrongly,  under  the  name  of  the  principal 
symptoms,  chief  among  these  being  neurasthenia. 
It  does  not  seem  advisable,  at  this  stage  of  prog- 
ress, to  make  any  hard  and  fast  statements,  hence 
all  that  may  be  said  here  to-night  will  be  purely 
suggestive,  the  prospective  value  of  such  proced- 
ures as  may  be  mentioned  being  left  to  the  judg- 
ment of  those  who,  being  convinced  of  the  reason- 
able basis  outlined,  may  be  sufficiently  interested 
to  put  them  to  the  test. 

There  seem  to  be  fashions  in  medical  matters 
just  as  there  are  in  dress  or  art.  If  I  am  not  much 
mistaken  it  is  beginning  to  be  the  fashion  to  study 
and  write  about  the  internal  secretions.  A  number 
of  books  have  appeared  on  this  subject.  I  even 
plead  guilty  to  having  written  one  on  the  thera- 
peutics of  the  internal  secretions.  There  are,  with- 
out the  least  exaggeration,  thousands  of  papers  on 
the  various  phases  of  this  fascinating  subject  pub- 
lished in  practically  every  quarter,  chiefly  however 
in  French,  Russian,  and  Italian. 

All  this  is  as  it  should  be,  for  from  all  sides  come 


IN  PRACTICAL  MEDICINE  165 

words  of  commendation  and  evidences  of  profound 
interest,  and  every  interested  physician  that  I  have 
had  the  pleasure  of  meeting  in  half  a  dozen  differ- 
ent countries  has  manifested  an  unwonted  enthusi- 
asm in  his  investigation  of  this  subject — it  breeds 
enthusiasm,  for  so  often  we  stumble  across  the 
most  startlingly  wonderful  things  which  when 
they  are  first  published  abroad  are  usually  greeted 
with  the  smile  of  scorn,  just  as  were  Roentgen's 
remarkable  rays,  or  Marconi's  equally  amazing  dis- 
covery, or  Alexander  Graham  Bell's  wonderful  in- 
vention, by  which  all  of  us  have  profited  so  much. 
Sir  William  Osier  told  me  only  a  short  time  ago 
when  I  visited  him  at  Oxford  that  surgery  had 
been  having  its  innings  for  the  past  ten  years  or 
more  and  it  was  time  for  medicine  to  have  its  turn 
and  probably  the  "bat"  would  be  the  internal  se- 
cretions of  the  ductless  glands.  For  instance,  what 
surgical  discovery  excels  in  its  scope  and  wonder 
the  many-sided  usefulness  of  pituitary  extract? 

In  these  days  of  advance  in  physiological  and 
pathological  research  we  have  gradually  accumu- 
lated a  fair  knowledge  of  the  series  of  organs  which 
were  until  recently  almost  entirely  unknown.  We 
have  learned  that  the  ductless  glands  or  endocrin- 
ous organs  exercise  an  intimate  control  over  met- 
abolism and  the  celluar  activities,  that  this  is  in 
all  probability  brought  about  by  definite  chemical 
substances  produced  in  these  organs  and  conveyed 
from  them  to  others  by  means  of  the  blood  and 


166  THE  INTERNAL  SECRETIONS 

lymph — the  "hormones,"  so  named  by  Starling  in 
1902 — and,  best  of  all,  that  it  is  possible  to  secure 
from  animal  glands  certain  active  hormone-bear- 
ing substances  in  a  more  or  less  pure  state  which 
are  available  in  the  treatment  of  the  disease. 

We  cannot  stop  to  consider  the  occasional  state- 
ments to  the  effect  that  organotherapy  is  a  fad,  or 
that  it  is  still  in  its  infancy  and  hence  not  worthy 
of  more  than  passing  consideration,  and  that  much 
more  work  will  have  to  be  done  before  the  subject 
reaches  a  really  practical  stage.  Those  who  mani- 
fest such  sentiments  invariably  make  their  state- 
ments without  deliberation  and  due  consideration 
of  the  facts.  None  can  deny  that  certain  of  the 
ductless  glands  produce  extremely  active  principles 
which  have  an  equally  active  influence  in  the  con- 
trol of  normal  as  well  as  morbid  phenomena.  We 
have  only  to  recall  the  influence  of  thyroid  extract 
in  myxedema,  adrenalin  in  local  hemorrhage,  or 
pituitary  extract  in  labor  to  realize  that  there  are 
sufficient  inducements  to  delve  more  deeply  into 
the  studv  of  the  extracts  of  these  organs,  as  well 
as  of  others  known  to  be  concerned  in  the  main- 
tenance of  what  is  now  termed  "the  hormone  bal- 
ance." 

This  factor  deserves  much  more  consideration 
than  it  is  possible  to  give  it  this  evening,  for  the 
delicate  balance  brought  about  by  the  interrelation 
of  the  internal  secretions  is  concerned  in  the  main- 
tenance of  essential  health  none  the  less  than  in 


IN  PRACTICAL  MEDICINE  167 

the  production  of  deviations  therefrom.  I  am  go- 
ing to  propound  what  I  believe  to  be  an  axiom — it 
is  impossible  for  an  individual  to  manifest  the  re- 
sults of  chronic  disease  without  a  corresponding 
disturbance  in  some  or  all  of  these  hormone-pro- 
ducing organs.  Further  than  that,  I  believe  that 
many  of  these  intractable  symptoms-complex,  to 
which  it  is  sometimes  so  difficult  to  give  a  suitable 
name,  are  often  aggravated  by  a  disturbance  in 
what  has  been  termed  the  "altruistic  function"  of 
the  cell.  I  will  explain:  Campbell  considers  that 
cell  activity  is  properly  divided  into  the  egoistic 
and  the  altruistic  cell  functions.  The  former  con- 
sists in  the  maintenance  of  individual  cell  activity, 
while  the  latter  concerns  the  supply  to  the  organ- 
ism as  a  whole  of  certain  services,  probably 
brought  about  by  the  hormones,  such  as  are  ex- 
emplified in  the  numerous  functional  relationships 
between  organs.  This  altruistic  function  is  of  ex- 
treme importance,  for  the  cell  itself  may  seem  to 
all  intents  and  purposes  quite  healthy  and  yet  still 
gravely  fail  in  its  altruistic  functioning — a  failure 
which,  small  though  it  be,  may  suffice  to  disorgan- 
ize the  delicate  hormonic  balance.  Granting,  then, 
that  chronic  disturbances  are  associated  with  gen- 
eral cellular  inactivity  and  that  in  certain  condi- 
tions this  deprives  the  body  of  essential  stimuli, 
it  must  be  obvious  that  the  effective  treatment  of 
such  conditions  must  include  a  consideration  of  the 
ductless  glands  and  of  means  capable  of  re-estab- 


168  THE  INTERNAL  SECRETIONS 

lishing  the  normal  production  of  their  hormones. 

One  of  the  most  common  disorders  in  which  so- 
called  "pluriglandular  insufficiency"  is  evident  is 
neurasthenia,  in  which  there  may  be  no  positive 
evidence  of  defective  action  of  a  gland  or  series  of 
glands.  It  is  obvious  that  in  the  majority  of  such 
cases  there  must  be  a  disturbed  endocrinism,  for  it 
is  hardly  reasonable  to  suppose  that  in  an  individ- 
ual with  prominent  manifestations  of  half-speed 
function,  such  as  constant  fatigue  on  slight  exer- 
tion, defective  oxidation  as  evidenced  by  low  urin- 
ary solids,  nerves  that  are  easily  set  "on  edge,"  cir- 
culation that  is  poor,  with  cold,  clammy  extremi- 
ties, and  not  infrequently  reduced  tension,  ambi- 
tion and  mental  powers  much  below  par,  and  the 
like,  the  production  of  the  essential  chemical  mes- 
sengers is  not  reduced  just  as  are  all  the  body  activ- 
ities. This  being  the  case,  pluriglandular  therapy 
not  only  serves  to  replace,  in  however  slight  de- 
gree, the  missing  secretions,  but  favors  an  in- 
creased production  of  them  by  the  homostimulant 
action  already  referred  to. 

Theoretically  this  sounds  very  plausible  and 
practically  it  has  been  found  to  work  very  nicely. 
Pluriglandular  therapy  is  undoubtedly  empirical, 
for  in  the  class  of  cases  under  discussion  at  least, 
there  is  no  definite  proof  as  to  which  of  the  ductless 
glands  is  deficient  and  to  what  extent.  For  this 
reason  it  has  been  ridiculed  by  some  who  forget 
that  nine-tenths  of  our  present  therapeutics  was  at 


IN  PRACTICAL  MEDICINE  169 

one  time  purely  empirical,  while  a  good  share  of 
it  still  has  no  positive  scientific  basis.  A  procedure 
that  has  secured  results  before  may  do  so  again, 
hence  it  is  worth  trying.  This  is  the  present  posi- 
tion of  pluriglandular  therapy,  and  it  is  believed 
that  the  successes  already  obtained  are  an  earnest 
of  what  is  in  prospect. 

Another  important  series  of  chronic  conditions 
which  must  at  least  be  mentioned  in  passing  are 
the  functional  neuroses  and  psychoses,  many  of 
which  are  now  earmarked  as  resulting  from  or  be- 
ing intimately  associated  with  disordered  secre- 
tory action  of  certain  of  the  ductless  glands.  In  a 
recent  paper  in  the  American  Journal  of  Insanity, 
Murray  Auer  concludes  that  the  glands  of  internal 
secretion  mutally  influence  functional  activity  and 
the  occurrence  of  insanity  at  puberty  and  adoles- 
cence, after  severe  physical  and  mental  strain,  and 
at  the  time  of  the  menopause  (all  periods  when  the 
metabolic  changes  of  the  body  are  intense),  and 
the  occurrence  of  syndromes  unquestionably  the 
result  of  disease  of  the  endocrine  organs,  insan- 
ity, idiocy,  debility,  mania  and  dementia,  suggest 
strongly  that  the  true  etiology  of  the  affective  psy- 
choses lies  in  functional  disturbances  of  the  glands 
of  internal  secretion. 

Many  of  the  problems  of  the  medical  gynecolo- 
gist have  an  altogether  endocrine  origin,  and  the 
metabolic  disturbances  of  women  constitute  a  large 
class  of  chronic  diseases  in  which  organtherapy  is 


170  THE  INTERNAL  SECRETIONS 

an  extremely  useful  measure.  Substitutive  organo- 
therapy is  an  every-day  measure  of  the  most  pro- 
gressive gynecologists  and  the  subject  is  far  too 
large  to  discuss  here.  The  value  of  the  extracts  of 
the  corpus  luteum  in  ovarian  hypofunction,  as  well 
as  the  homostimulant  action  of  the  same  substance 
in  less  serious  conditions,  is  becoming  increasingly 
apparent.  Pituitary  extract  is  now  used  in  a  great 
many  cases  of  this  class,  not  merely  for  its  obstet- 
rical virtues  but  as  a  means  of  re-establishing  a 
disturbed  balance  in  cases  like  amenorrhea  and  cer- 
tain forms  of  dysmenorrhea. 

One  of  the  most  neglected  organotherapeutic 
remedies  in  gynecological  practice  is  the  extract  of 
the  mamma,  about  which  I  cannot  refrain  from  say- 
ing a  few  words.  Briefly,  the  mamma  is  also  an 
internal  secretory  organ  and  is  the  direct  antag 
onist  of  the  ovaries,  hence  extracts  thereof  may  be 
of  value  in  the  control  of  conditions  due  to  super- 
activity of  the  ovaries.  The  principal  among  these 
are  menorrhagia,  metrorrhagia,  and  uterine 
fibroids.  I  know  the  surgeons  will  disagree,  but 
the  fact  remains  that  functional  uterine  hemor- 
rhage (not  due  to  foreign  bodies  or  organic  condi- 
tions) is  frequently  controlled  better  by  a  course 
of  mammary  extract  than  by  any  other  means  and 
there  is  a  rational  physiological  reason  for  this 
benefit.  A  number  of  Russian  investigators  have 
shown  that  the  use  of  mammary  substance  is  of 
extreme  value  in  many  cases  of  fibroids  and  those 


IN  PRACTICAL  MEDICINE  171 

who  may  be  especially  interested  in  this  subject 
might  with  an  advantage  read  a  paper  which  I 
have  prepared  for  a  Special  Internal  Secretion  Is- 
sue of  the  Woman's  Medical  Journal  for  March, 
1915.*  Suffice  it  to  say  that  enough  evidence  is 
gathered  together  there  to  warrant  the  use  of 
mammary  extract  for  a  period  before  operative  pro- 
cedures are  taken  and  the  aggregate  results  are 
sufficiently  good  eventually  to  bring  this  method 
of  treatment  into  much  higher  esteem  and  fre- 
quent usage. 

[Within  the  past  year  (1917)  I  have  had 
occasion  indirectly  to  note  the  clinical  value  of  this 
phase  of  treatment  in  a  case  of  well-advanced  can- 
cer. A  colleague,  interested  in  organotherapy, 
was  recommended  to  try  mammary  substance  in 
a  case  of  uterine  carcinoma  in  an  old  woman.  There 
was  much  hemorrhagic  oozing,  as  well  as  very  bad 
odor.  Twenty  grains  of  mammary  substance  wrere 
administered  each  day  for  a  week  and  the  dose  then 
increased  to  30  grains.  The  treatment  was  sug- 
gested by  me  in  the  hope  that  the  oozing  which 
had  persisted  for  months  despite  various  internal 
and  local  treatments,  might  be  staunched.  I  was 
particular  to  emphasize  the  slimness  of  the  pros- 
pects and  that  the  method,  was  really  offered  as  a 
last  resort. 

Not  only  was  the  hemorrhage  stopped  but  the 
odor  was  considerably  diminished  and  the  patient 


*See  Chapter  XVI. 


172  THE  INTERNAL  SECRETIONS 

even  began  to  assure  her  family  that  she  was  going 
to  get  well,  since  her  strength  really  did  improve 
quite  considerably.  The  doctor,  however,  took 
pains  to  inform  them  that  the  treatment  was 
merely  having  an  effect  upon  the  blood  supply  of 
the  affected  organ  and  not  upon  the  disease  itself, 
and  even  so  this  seemed  to  all  concerned  to  be  a 
very  distinct  vindication  of  the  anti-hemorrhagic 
effect  upon  the  uterus  of  mammary  substance.] 

You  will  note  that  I  have  said  nothing  about  the 
use  of  thyroid  extract  in  the  chronic  and  well- 
known  conditions  associated  with  thyroid  defi- 
ciency, nor  can  I  take  time  to  outline  the  advan- 
tages of  pituitary  extract  in  those  equally  chronic 
conditions  of  hypopituitarism.  In  fact,  organo- 
therapy is  principally  useful  in  chronic  disease, 
anyway,  and  to  consider  the  matter  as  thoroughly 
as  the  subject  deserves  would  keep  us  too  long. 

We  now  come  to  the  second  and  perhaps  the 
more  important  part  of  this  paper — the  relation  of 
the  glands  of  internal  secretion  to  cancer  and  the 
possibilities  of  organotherapy  in  this  condition. 
This  is  neither  the  place  nor  the  time  to  discuss 
the  physiological  basis  of  cancer  or  to  speculate 
upon  the  how  or  why  of  this  disease.  We  may, 
however,  enumerate  several  promising  and  quite 
thoroughly  substantiated  theories:  (1)  Cancer  is 
a  chronic  intoxication;  (2)  its  incidence  evidences 
the  lack  of  an  element  in  the  blood  which  permits 
cell  proliferation  at  a  point  of  particularly  lowered 


IN  PRACTICAL  MEDICINE  173 

resistance;  (3)  it  is  essentially  a  disease  of  senes- 
cence or,  as  Hastings  Gilford  has  termed  it,  "cell 
senilism. " 

Seven  or  eight  years  ago  many  hopes  were  raised 
following  the  publication  of  the  results  of  work 
done  by  Dr.  John  Beard  of  Edinburgh,  and  quite 
an  impetus  was  given  to  the  study  of  organother- 
apy in  cancer  because  of  the  fact  that  trypsin  was 
then  brought  forward  in  medical  and,  unfortu- 
nately, lay  magazines  as  "worthy  of  immediate 
trial  in  the  behalf  of  the  many  persons  to  whom  it 
offers  a  possible  chance  of  escape  from  an  other- 
wise inexorable  fate."  Seemingly  the  attention  ot 
the  public  was  drawn  prematurely,  for  there  has 
been  no  remarkable  reduction  in  the  mortality  sta- 
tistics nor  do  any  of  us  here  consider  that  pancre- 
atic ferments  are  more  than  an  incidental  measure 
of  relief  in  cancer. 

It  must  be  admitted,  however,  that  Beard's  work 
virtually  inaugurated  a  more  enthusiastic  and 
searching  consideration  of  organotherapy  in  can- 
cer and  while  we  have  advanced  many  steps  since 
1906  we  must  not  be  satisfied  yet.  In  the  words  of 
a  recent  writer:  "We  have  survived  too  many  hy- 
potheses in  regard  to  this  elusive  disease  to  accept 
further  generalizations  however  plausible  they 
may  be  at  first  inspection  of  the  evidence;  yet  we 
are  always  glad  to  recognize  every  scintilla  of  a 
new  suggestion  which  may  furnish  a  welcome 
guide  to  progress." 


174  THE  INTERNAL  SECRETIONS 

With  the  foregoing  in  mind  it  may  be  well  to  col- 
late a  number  of  ideas  which  indicate  a  relation- 
ship between  the  incidence  of  cancer  and  ductless 
gland  disorder,  so  that  we  may  use  them  as  a  foun- 
dation for  possible  lines  of  treatment  in  this  direc- 
tion. They  may  also  serve  as  a  basis  for  explain- 
ing the  not  infrequent  reports  of  the  good  results 
from  organotherapy  in  cancer  which  are  to  be 
found  in  the  literature. 

We  know  that  cellular  activity  is  influenced  by 
the  hormones,  or  chemical  messengers,  that  nutri- 
tion responds  in  a  greater  or  lesser  degree  to  their 
influence,  and  that  it  is  possible  to  favor  the  reac- 
tion of  the  body  against  disease  by  the  ingestion  of 
certain  organic  extracts.  The  first  question  which 
naturally  suggests  itself  is:  Is  not  cancer  more 
than  a  chronic  disease  such  as  the  more  benign 
metabolic  disturbances  previously  referred  to?  Is 
it  possible  to  influence  by  means  of  organotherapy 
an  unquestionably  organic  condition  when  the  ac- 
tion of  the  endocrine  principles  is  supposed  to 
be  upon  function  rather  than  upon  structure?  Un- 
doubtedly no  form  of  internal  medication  at  pres- 
ent known  will  destroy  or  remove  the  fundamental 
organic  conditions  pathognomonic  of  cancer,  but 
it  is  entirely  possible  that  the  resistance  of  the  suf- 
ferer from  cancer  may  be  increased  to  such  a  de- 
gree that  other  measures  in  common  use  may  be 
backed  up  by  an  increase  in  the  responsiveness  of 
the  cells  and  a  general  enhancement  of  nutrition. 


IN  PRACTICAL  MEDICINE  175 

Some  individuals,  for  reasons  at  present  only 
premised,  present  a  special  receptivity  to  the  im- 
plantation and  growth  of  cancer  cells.  Why  this 
should  be  so  and  just  how  the  cells  become  im- 
planted is  not  for  us  to  consider  here,  although  it 
is  a  very  fascinating  subject  and  will,  I  believe, 
some  day  be  thoroughly  elucidated.  I  think  it 
will  be  found  to  be  much  more  intimately  concerned 
with  the  internal  secretions  than  is  at  present  gen- 
erally believed. 

Clinically,  the  one  essential  symptom  of  cancer 
is  waning  cellular  activity.  Almost  invariably  nu- 
trition is  poor  and  with  few  exceptions  cancer  is 
limited  to  individuals  past  the  prime  of  life,  a  fact 
which  indicates  there  may  be  a  direct  connection 
between  the  activity  of  those  organs  of  internal  se- 
cretion whose  work  ceases  at  this  period  and 
whose  action  is  no  longer  needed.  Experimentally 
it  seems  to  be  proved  that  there  is  a  basis  for  the 
idea  that  the  susceptibility  to  the  implantation  of 
the  cancer  cells  is  in  some  way  related  to  the 
gonads  and  evidence  of  this  is  to  be  found  in  the 
investigations  of  Sweet,  Corson-White,  and  Saxon 
of  Philadelphia,  who  found  that  when  tumors  were 
transplanted  into  animals  (mice)  which  had  previ- 
ously been  castrated  the-  frequency  of  the  estab- 
lishment of  the  cancerous  implant,  as  well  as  the 
rapidity  of  its  proliferation,  was  considerably  more 
noticeable  in  the  animals  that  were  thus  rendered 
more  susceptible. 


176  THE  INTERNAL  SECRETIONS 

If  we  admit  that  an  important  factor  in  all  can- 
cer cases  is  chronic  cellular  intoxication,  then  ob- 
viously a  part  of  the  treatment  consists  in  favor- 
ing the  activity  of  the  known  detoxicating  organs 
as  well  as  removing  all  nidi  of  further  trouble, 
chiefly,  of  course,  in  the  alimentary  canal.  The 
thyro-parathyroid  apparatus  is  intimately  con- 
cerned in  the  destruction  of  toxins  and  it  is  not  re- 
markable to  find  a  number  of  references  in  the  lit- 
erature to  the  fact  that  in  cancer  subjects  the  thy- 
roid is  usually  found  to  be  more  or  less  atrophied. 
Parenthetically,  it  may  be  remarked  that  thyroid 
hypofunction  is  very  much  more  common  than 
until  recently  has  been  believed,  and  it  is  entirely 
possible  for  the  thyroid  cells  to  be  seemingly  nor- 
mal from  a  pathological  standpoint  and  yet  be 
failing  very  materially  in  the  production  of  those 
substances  which  are  responsible  for  the  carrying 
out  of  the  "altruistic  work"  of  this  gland.  Of  course 
there  has  been  considerable  opposition  to  any  the- 
ory which  definitely  connected  the  thyroid  with 
this  disease  for  thyroid  therapy  will  be  found  to 
have  practically  no  influence  at  all  upon  cancer. 

The  association  of  intestinal  fermentation,  how- 
ever, has  long  been  observed  in  cancerous  indi- 
viduals and  has  even  formed  the  basis  of  several 
theories  as  to  its  etiology.  One  of  the  well  known 
manifestations  of  the  cancerous  cachexia  is  achlor- 
hydria  and  the  resulting  digestive  disabilities.  For 
this  reason  I  recommend  as  a  reasonable  organo- 


IN  PRACTICAL  MEDICINE  177 

therapeutic  procedure  in  all  cases  of  cancer  the  at- 
tempt to  re-establish  the  activties  of  the  digestive 
glands  by  the  administration  of  secretin.  This  ali- 
mentary hormone,  secured  from  the  duodenal 
walls,  is  a  physiological  means  of  stimulating  the 
functionally  inactive  glands  of  the  pancreas,  liver, 
and  intestines.  Another  sound  reason  for  this  par- 
ticular adjunct  measure  lies  in  the  fact  that  the  ab- 
sence of  HC1  from  the  stomach  removes  the  normal 
stimulus  to  secretin  production,  since  prosecretin 
is  converted  into  secretin  and  released  from  the 
duodenal  walls  only  by  contact  with  the  acid 
chyme,  which  is  practically  always  absent  in  can- 
cer. Further,  since  the  action  of  secretin  is  not 
limited  to  the  digestive  glands  themselves,  but  also 
distinctly  favors  the  production  of  secretin  in  the 
duodenum  itself,  its  value  should  be  doubly  evi- 
dent, and  the  advantages  accruing  from  the  en- 
hanced digestion  resulting  from  this  procedure  re- 
duce the  toxemia  normally  present  in  cancer  and 
at  least  must  be  considered  one  factor,  even  though 
a  small  one,  in  the  treatment  of  this  disease. 

The  second  of  the  postulates  previously  set  forth 
suggests  the  absence  from  the  body  of  a  certain 
element,  or  series  of  elements.  Just  what  is  miss- 
ing from  the  blood  of  the  cancerous  is  not  yet  well 
known,  although  the  work  of  Abderhalden  and 
those  his  research  has  stimulated  indicates  a  defi- 
nite series  of  substances  may  be  concerned  in  this 
matter.     Weiss  has  gone  so  far  as  to  show  that 


178  THE  INTERNAL  SECRETIONS 

serodiagnostic  tests  demonstrate  an  opposite  be- 
havior on  the  part  of  the  serum  from  cancer  pa- 
tients and  normal  serum,  and  that  this  definite  lack 
permits  cancer  cells  to  proliferate,  principally  at 
parts  exposed  to  mechanical  stress  or  irritation. 
He  even  suggests  it  may  be  possible  to  isolate  from 
normal  serum  the  element  in  question,  the  lack  of 
which  permits  malignant  proliferation,  and  utilize 
this  in  the  prophylaxis  and  treatment  of  cancer. 
However  near  this  may  be  to  the  truth,  it  will  ob- 
viously be  an  extremely  difficult  matter  to  make 
practical  use  of  it,  at  least  to  any  considerable  ex- 
tent, and  we  must  look  still  further  for  encourage- 
ment. This  missing  element,  to  my  mind,  will 
likely  be  found  to  be  produced  by  the  endocrine 
system,  and,  since  the  evidence  already  deduced 
indicates  that  his  is  not  an  unreasonable  premise, 
the  therapeutic  possibilities  are  materially  in- 
creased, for  we  now  know  with  considerable  cer- 
tainty that  when  there  is  a  functional  hypoendo- 
crinism  or  reduction  in  activity  or  service  to  the 
body  of  certain  of  the  internal  secretory  organs, 
not  only  can  the  missing  substances  be  replaced, 
but  the  semi-active  organs  may  be  stimulated  by 
certain  organic  extracts  in  accordance  with  Hal- 
lion's  law  of  homostimulation:  "Extracts  of  an 
organ  exert  on  the  same  organs  an  exciting  influ- 
ence which  lasts  for  a  longer  or  shorter  time.  When 
the  organ  is  insufficient  it  is  conceivable  that  this 
influence  augments  its  action  and,  when  it  is  in- 


IN  PRACTICAL  MEDICINE  179 

jured,  that  it  favors  its  restoration. "  Resulting 
from  these  and  similar  premises  quite  a  number  of 
attempts  have  been  made  to  use  organic  extracts 
alone  and  in  various  combinations  as  a  part  of  the 
treatment  of  cancer.  While  we  have  not  yet  found 
an  ideal  remedy,  it  seems  certain  that  organic  ex- 
tracts do  produce  beneficial  results  of  varying  de- 
gree. 

The  spleen  and  thymus  offer  probably  greater 
possibilities  than  many  of  the  other  glands,  al- 
though I  think  that  eventually  the  optimum  prep- 
aration will  be  a  pluriglandular  extract  containing 
these  and  other  synergists.  The  therapeutic  ad- 
ministration of  spleen  extract  increases  nutrition, 
of  that  I  am  quite  convinced,  and  those  who  have 
followed  the  work  of  Bayle  of  Cannes  in  the  use 
of  spleen  emulsions  and  extracts  in  the  treatment 
of  tuberculosis  cannot  but  be  convinced  that  there 
is  good  reason  for  his  success.  His  report  to  the 
International  Congress  on  Tuberculosis  in  Rome  is 
extremely  interesting.  I  have  personally  had  a 
number  of  communications  from  this  gentleman, 
as  we  have  for  some  years  been  mutually  interested 
in  each  other's  work,  and  when  the  war  started  he 
was  engaged  in  translating  my  book  into  French. 

Bayle's  explanation  of  the  sometimes  remark- 
able influence  of  spleen  extract  is  based  upon  what 
he  calls  its  "colloidogenic"  action.  His  theory  is 
this:  The  blood  contains  the  mineral  elements  in 
two  forms — (1)  Those  in  a  colloid  state  suitable 


180  THE  INTERNAL  SECRETIONS 

for  cellular  appropriation,  and  thus  not  suited  for 
elimination  by  the  kidneys,  and  (2)  the  mineral 
cellular  wastes,  which  are  dissolved  in  the  plasma, 
and  are  destined  to  be  eliminated.  If  the  colloid 
elements  lose  their  colloidal  form  they  are 
promptly  eliminated  and  a  condition  of  demineral- 
ization  obtains.  The  capacity  to  maintain  the  min- 
eral salts  in  a  colloidal  state  is  evidently  of  consid- 
erable importance,  and,  according  to  Bayle,  seems 
to  belong  to  the  spleen.  Bayle  states  that  he  has 
always  found  that  splenic  opotherapy  quickly  re- 
duces an  excessive  elimination  of  phosphates  in 
the  urine.  All  of  this  deserves  to  be  tested  experi- 
mentally and  clinically. 

Now,  there  is  undoubtedly  a  condition  of  min- 
eral starvation  in  all  cachectic  states,  including 
that  of  cancer.  This  has  been  frequently  mentioned 
in  the  literature,  and  is  referred  to  in  an  editorial 
in  the  Journal  of  the  American  Medical  Associa- 
tion in  the  following  words:  "This  is,  however, 
little  less  than  the  metabolic  story  of  partial  inani- 
tion which  attends  the  cachectic  states  which  ac- 
company so  many  chronic  diseases.  The  demin- 
eralization,  that  is,  the  gradual  and  undue  loss  of 
all  inorganic  elements  from  the  organism,  is  like- 
wise not  to  be  regarded  as  characteristic  of  cancer 
alone."  This  is  admitted,  for  one  of  the  principal 
manifestations  of  tuberculosis  is  this  very  condi- 
tion, which  explains  Bayle's  suggestions  and  his 
successful  application  of  splenic-opotherapy  in  the 


IN  PRACTICAL  MEDICINE  181 

treatment  of  tuberculosis.  There  is  no  reason, 
however,  why  the  same  fundamentals  should  not 
be  as  applicable  in  the  therapy  of  cancer  as  of  tu- 
berculosis, and  this  may  be  an  explanation  of  the 
good  results  occasionally  reported  from  the  use  of 
spleen  extract. 

Another  gland  frequently  classed  with  the 
spleen,  or  at  least  with  the  lymphatic  glands,  is 
the  thymus  and  more  clinical  work  seems  to  have 
been  done  with  thymus  extract  in  cancer  than  with 
any  other  single  extract.  In  1907  Dwyer  reported 
a  number  of  cases  that  were  benefited  by  this  form 
of  treatment  and  the  more  recent  experimental  re- 
searches of  Rodenburg,  Bullock,  and  Johnson,  of 
this  city,  seem  to  prove  that  the  products  of  the 
ductless  glands  are  destined  to  play  a  certain  role 
in  our  fight  against  cancer,  and  their  recommenda- 
tions include  the  use  of  thyroid,  thymus,  and  other 
extracts  as  part  of  the  treatment. 

Some  very  interesting  work  in  the  study  of  can- 
cer has  been  done  by  Dr.  Seelye  W.  Little  of  Roch- 
ester, N.  Y.,  and  as  a  result  of  this  he  outlines  cer- 
tain facts  which  he  has  inferred  from  quite  a  num- 
ber of  clinical  experiences.  In  the  main  his  con- 
tention is  that  the  reproduction  of  the  reverted  cell 
types  in  cancer  is  caused  by  the  relative  hypofunc- 
tion  of  certain  of  the  ductless  glands  and  that  to 
produce  a  cancerous  growth  such  hypofunction 
must  be  primarily  in  an  internal  secretory  organ 
derived  from  the  same  blastodermic  layer  as  are 


182  THE  INTERNAL  SECRETIONS 

the  cells  from  which  the  cancer  originates.  As  a 
result  of  this  he  suggests  that  mammary  carcinoma 
implies  hypofunction  of  some  endocrine  organ  de- 
rived from  the  ectoderm,  since  the  breast  is  ecto- 
dermic  in  origin.  He  has  also  shown  that  the  met- 
abolism of  sugar  and  calcium  are  intimately  con- 
nected with  the  disordered  nutrition  of  cancer  and 
connects  this  in  a  very  convincing  manner  with 
those  glands  which  exert  a  vital  relation  to  the 
metabolism  of  sugar  or  calcium  or  both. 

Little's  experiences  are  fascinatingly  outlined  in 
his  papers  published  in  the  Boston  Medical  and 
Surgical  Journal  last  year,  to  which  the  careful 
attention  of  every  student  of  this  subject  should  be 
drawn.  His  clinical  findings  warrant  the  use  of 
several  organic  extracts,  principally  from  the  pitu- 
itary, parathyroid,  adrenal  cortex  and  the  islands 
of  Langerhans.  In  his  most  recent  paper,  in  addi- 
tion to  emphasizing  the  value  of  sugar  feeding  in 
many  cases  of  cancer,  he  has  settled  down  to  three 
ductless  gland  extracts  as  essential,  one  each  for 
ectodermic,  mesodermic,  and  endodermic  cancer. 
For  the  first  he  uses  total  pituitary  extract;  for  the 
second  an  extract  of  the  adrenal  cortex;  and  for 
the  third  an  extract  of  the  pancreas  rich  in  the 
islands  of  Langerhans.  All  through  his  communi- 
cations there  is  an  underlying  element  of  judicial 
research.  He  is  not  ultra  enthusiastic  and  does  not 
claim  to  have  discovered  a  panacea  for  cancer.  One 
cannot  but  believe  from  the  clinical  results  of  his 


IN  PRACTICAL  MEDICINE  183 

work' that  he  is  on  the  right  track  and  that  the  con- 
clusions which  may  be  drawn  from  some  of  the 
facts  gathered  together  here  this  evening  warrant 
the  continued  investigation  by  a  much  larger  num- 
ber of  students  of  the  subject,  not  only  of  the  rela- 
tions of  the  ductless  glands  to  the  incidence  of  can- 
cer, but  the  prophylactic  and  direct  treatment 
thereof  by  organotherapy. 

The  third  essential  concerns  the  relation  of  the 
incidence  of  cancer  to  senility.  We  cannot  deny 
that  senility  is  the  result  of  changes  in  certain  of 
the  internal  secretory  organs  and  that  by  far  the 
greatest  cancer  incidence  will  be  found  in  individu- 
als well  past  the  apex  of  vital  activities.  Just  as 
fungus  growths  are  usually  found  on  decaying 
trees,  so  the  similar  cancerous  manifestations  are 
evidences  of  senile  decay.  Dr.  Hastings  Gilford  of 
Reading,  England,  writes  occasionally  on  the  vari- 
ous subjects  connected  with  senility  and  the  duct- 
less glands,  and  while  at  times  he  delves  deeper 
than  I  am  able  to  fathom,  he  is  undoubtely  cor- 
rect in  his  theories  regarding  cancer,  that  it  is 
essentially  a  form  of  cell  senility.  He  says  that 
"certain  somatic  cells  become  dead  while  the  tissue 
around  them  is  still  in  a  state  of  comparative  youth. 
They  express  their  senility  by  returning  to  a  more 
embryonic  form  and  as  they  do  so  they  increase  in 
number,  the  faculty  of  proliferation  being  one  of 
the  manifestations  of  regression."  These  senile 
changes  may  be  presumed  to  be  connected  with 


184  THE  INTERNAL  SECRETIONS 

disturbances  in  the  hormone  balance. 

This  brings  us  to  the  consideration  of  another 
important  phase  of  this  subject — whether  it  is  pos- 
sible to  use  these  organic  extracts  as  prophylactic 
agents.  I  think  it  may  be,  but  it  is  very  difficult  to 
know  how  and  when  to  begin,  for  usually  patients 
suffering  with  cancer  do  not  give  us  the  oppor- 
tunity of  investigating  their  trouble  until  the  dis- 
ease is  well  established. 

Dr.  Robert  Bell  of  London  has  written  telling 
"How  to  Destroy  the  Cancer  Scourge,"  and  aims 
to  do  this  by  restoring  the  vital  energies  of  the 
whole  cellular  structure  by  what  he  considers  to  be 
a  suitable  diet.  Unfortunately,  however,  recourse 
to  this  diet  does  not  seem  to  have  become  the 
fashion  yet,  and  the  scourge  is  not  being  destroyed. 
The  cancerous  individuals  are  always  run  down; 
they  are  in  a  state  of  receptivity  to  disease  and  are 
obviously  sufferers  from  pluriglandular  insuffi- 
ciency. If  this  subject  is  more  carefully  studied — 
it  is  remarkable  how  extended  are  its  ramifications 
and  how  practical  are  the  resulting  clinical  deduc- 
tions— the  reasonableness  of  this  position  may  be 
clear  to  you.  In  other  words,  suitable  combinations 
of  glandular  substances  may  be  given  empirically 
where  a  more  or  less  obvious  deficiency  is  pre- 
sumed. 


XV 

SOME  REMARKS  ON  THE  TREATMENT  OF 
HYPERTHYROIDISM 


THE  editorial  invitation  extended  in  a  recent  is- 
sue of  Clinical  Medicine,  to  "throw  more  light  on 
this  subject"  of  hyperthyroidism,  prompts  the  fol- 
lowing remarks,  which,  it  is  hoped,  may  be  of  inter- 
est because  of  the  numerous  and  widely  differing 
measures  suggested  in  current  medical  literature 
for  the  treatment  of  thyrotoxicosis,  or  hyperthy- 
roidism. 

To  my  mind,  there  are  three  important  things  to 
accomplish  or  to  attempt  to  accomplish  in  the  treat- 
ment of  this  troublesome  condition;  namely: 

First,  the  control  of  the  toxemia,  and  especially 
of  its  serious  cardiac  manifestations; 

Second,  the  removal  of  the  sundry  and  widely 
differing  causes  of  the  thyroid  irritability;  and 

Lastly,  the  re-establishment  of  the  deranged 
metabolism  and  the  "building  up"  of  the  badly  dis- 
organized cell  nutrition. 

The  immediate  treatment  of  cases  of  hyperthy- 
roidism, in  my  estimation,  centers  on  the  control  of 
the  heart's  action;  and  this  is  accomplished  most 
satisfactorily  by  placing  the  patient  at  absolute  rest 
in  bed,  in  a  quiet  room  away  from  the  numerous 


Reprinted  from  The  American  Journal  of  Clinical  Medicine 
(Chicago),  April,  1917. 

(185) 


186  THE  INTERNAL  SECRETIONS 

worries  and  noises  of  the  home.  Cold  applications 
over  the  region  of  the  heart  and  of  the  thyroid 
gland  exert  some  beneficial  effect. 

By  far  the  most  important  remedy,  in  my  expe- 
rience, is  the  extract  of  the  posterior  lobe  of  the 
pituitary,  which  may  be  given,  by  intramuscular 
injection,  daily  in  doses  of  a  1-2  to  1  mil  (Cc.)  of 
the  usual  standard  solution.  I  have  had  occasion 
to  use  numerous  sedative  remedies,  and  none 
seemed  to  exert  so  particularly  beneficial  an  effect 
as  this  organotherapeutic  wonderworker. 

The  usual  effect  of  these  injections  is,  the  reduc- 
tion of  the  pulse  rate  by  from  30  to  70  beats  a  min- 
ute, while,  by  its  remarkable  influence  upon  so 
many  functions,  it  also  favors  the  intestinal  activi- 
ties as  well  as  increasing  diuresis.  According  to 
Pal,  the  principle  of  the  posterior  pituitary  lobe  ap- 
pears actually  to  exert  a  well-defined  antagonistic 
action  upon  the  unruly  thyroid  gland.  Whether 
the  pituitary  gland  contains  a  principle  that  exerts 
an  effect  opposite  to  that  of  the  thyroid  gland  (an 
antihormone),  has  not  been  established;  still,  I  am 
convinced  that,  clinically  at  least,  pituitary  therapy 
is  as  profitable  an  advance  in  the  treatment  of  hy- 
perthyroidism as  is  any  measure  suggested  in  the 
past  and  deserves  much  wider  application  and 
study  in  practice.  This  matter  will  be  referred  to 
again  shortly. 

Since  it  is  imperative  to  accomplish  some  imme- 
diate   and    tangible    results    by    the    symptomatic 


IN  PRACTICAL  MEDICINE  187 

treatment  of  the  patient  and  particularly  the  heart's 
action,  it  is  in  order  carefully  to  investigate  every 
possible  source  of  toxemia  and  to  antagonize  it  to 
the  best  of  our  ability.  Undoubtedly  the  most  fer- 
tile field  for  toxemia  is  the  intestinal  canal,  and  my 
routine  treatment  in  such  cases,  instead  of  resort- 
ing to  purging-treatment  by  mouth  (toxins  re- 
leased by  vigorous  purging  exert  a  very  unfortu- 
nate effect  upon  the  symptoms  and  have,  indeed, 
led  to  the  dismissal  of  the  physician  because  of  the 
severe  reaction  following  the  well-meant  and  none 
the  less  much-needed  treatment),  is  to  prescribe 
a  series  of  oil  enemata  administered  on  three  suc- 
cessive evenings.  These  enemata  should  consist  of 
5  or  6  ounces  of  any  convenient  oil  (cotton-seed, 
olive,  almond),  warmed  to  the  body-temperature 
and  injected  with  an  ordinary  bulb-syringe,  being 
made,  by  position  and  gravity,  to  reach  the  farthest 
end  of  the  large  intestine.  This  injection  is  to  be 
retained  all  night.  It  has  been  found  that  its  repe- 
tition on  the  second  and  third  nights  may  bring 
away  still  more  impacted  material  that  was  not 
loosened  by  the  first  one. 

Parenthetically  I  will  mention  that  many  sub- 
jects of  hyperthyroidism  have  an  associated  condi- 
tion that  might  properly  be  called  mild  mucous 
colitis,  and  I  am  beginning  to  believe  that  there 
subsists  a  distinct  relation  between  this  disease  and 
serious  endocrine  disturbances.  At  all  events,  where 
intestinal  irritability  is  discovered  and  the  patient 


188  THE  INTERNAL  SECRETIONS 

has  been  passing  more  or  less  mucus,  1  ounce  of 
the  pint  of  oil  may  be  replaced  by  1  ounce  of  ich- 
thyol  (or,  as  I  have  been  using  more  recently, 
ichthyonat),  which  suffices  to  soothe  the  intestinal 
wall  while  it  also  exerts  a  certain  degree  of  anti- 
septic action. 

If  laxatives  are  prescribed,  they  must  be  of  the 
gentlest-acting  nature.  Cathartic  pills,  pills  of  aloin, 
belladonna  and  strychnine,  and  active  alkaloid- 
containing  stimulants  are  not  advisable,  because  of 
their  vigorous  action  and  also  because  of  a  fre- 
quently undesirable  simultaneous  effect  upon  the 
heart. 

The  next  procedure  consists  in  neutralizing  the 
alimentary  toxemia  as  far  as  possible  and,  at  the 
same  time,  since  it  has  been  demonstrated  beyond 
question  that  the  majority  of  the  alimentary  wastes 
are  acid  in  reaction,  alkaline  treatment  is  in  order. 
It  is  my  custom  to  direct  the  patient  to  drink  dur- 
ing the  twenty-four  hours  at  least  3  pints  of  water 
in  which  from  60  to  100  grains  of  sodium  bicarbo- 
nate is  dissolved,  but  laying  strong  emphasis  on 
the  necessity  for  not  taking  any  of  the  alkaline 
water  within  one  hour  before  or  three  hours  after 
meals.  If  a  2-quart  Mason  jar  is  filled  three-fourths 
full  with  water  and  the  soda  is  dissolved  in  it,  not 
only  does  it  facilitate  the  measurement,  but  the 
sight  of  it,  in  a  conspicuous  place,  serves  as  a  re- 
minder, toward  the  close  of  the  day,  whenever  the 
patient  has  not  been  drinking  the  amount  ordered. 


IN  PRACTICAL  MEDICINE  189 

Furthermore,  the  fact  that  the  water  contains  a 
prescribed  remedy  and  the  reason  for  its  adminis- 
tration has  been  made  clear,  prompts  the  patient  to 
overcome  any  difficulty  he  may  experience  in  dis- 
posing of  this  quantity  (unfortunately,  it  is  not  the 
rule,  in  these  cases  at  least,  to  drink  sufficient 
water),  for  he  realizes  that  it  is  not  merely  the 
drinking  of  water  but  the  following  out  of  a  part 
of  the  doctor's  course  of  treatment.  In  addition  to 
the  foregoing,  I  frequently  have  prescribed  the 
combined  sulphocarbolates  as  a  means  of  keeping 
the  intestine  as  nearly  aseptic  as  possible.  The  dose 
should  be  at  least  30  grains  a  day;  however,  it 
seems  poor  policy  to  waste  good  medicine  of  this 
character  by  not  first  giving  the  intestine  a  thor- 
ough cleaning  out.  In  other  words,  the  sulpho- 
carbolate  tablets  must  not  be  prescribed  until  the 
fourth  day  of  treatment. 

Occasionally  in  severe  cases  there  is  a  more  or 
less  intractable  diarrhea,  and  for  the  control  of  this 
feature  I  have  been  using  protan  with  success. 

The  intestine  by  no  means  is  the  only  source  of 
toxic  substances  that  irritate  the  thyroid  gland. 
Thus,  it  has  been  found  quite  frequently  that  pyor- 
rhea is  an  accompanying  disturbance  in  these  cases, 
so  that  this  condition  must  be  treated  locally,  and 
thoroughly.  The  use  of  iodoglycerol  as  a  local  anti- 
septic and  as  an  indicator  of  "dirt"  on  the  teeth 
(which  latter  must  be  removed  mechanically)  is 
of  great  advantage.    Various  antiseptic  dentifrices 


190  THE  INTERNAL  SECRETIONS 

and  mouth-washes  profitably  may  be  recommended, 
while  I  have  seen  injections  of  emetine  bring  about 
very  favorable  effects,  not  merely  upon  the  amebi- 
asis, but  also  upon  the  thryoid  gland  and  its  func- 
tioning. 

Other  common  sources  of  irritation  of  the  thy- 
roid gland  are:  diseased  tonsils  and  infected  nasal 
sinuses  (frontal,  ethmoid  or  sphenoid),  pelvic  in- 
fections, and,  incidentally,  local  trouble  in  the 
angles  of  the  intestine,  the  gall-bladder,  and  else- 
where. 

The  doctrine  of  focal  infection  was  never  more 
applicable  and  practically  useful  than  in  the  "diag- 
nostic treatment"  of  thyroid  disorders,  and  many  a 
failure  satisfactorily  to  control  dysthyroidism  has 
been  owing,  not  so  much  to  inappropriate  treat- 
ment, as  to  the  fact  that  some  hidden  source  of 
toxemia  was  overlooked. 

Before  leaving  the  sources  of  thyroid  irritation, 
emphasis  must  be  laid  on  still  one  other  very  im- 
portant cause  of  functional  thyroid  troubles.  We 
are  now  convinced,  by  the  writings  of  Elliott  (Lon- 
don), Sergent  (Paris),  and  Cannon  (Boston),  that 
the  emotions  exert  a  specific  effect  upon  the  chem- 
istry of  the  body,  through  the  faculty  of  the  adrenal 
glands  to  respond  to  emotional  stimuli.  Fear,  rage, 
pain,  and  even  worry,  all  excite  the  chromaffin  sys- 
tem and  through  this  effect  cause  sensitization  or 
irritation  of  the  entire  sympathetic  mechanism. 

A  case  of  exophthalmic  goiter  is  on  record  which 


IN  PRACTICAL  MEDICINE  191 

developed  suddenly,  as  from  a  clear  sky,  immedi- 
ately following  the  mental  strain  imposed  by  the 
San  Francisco  earthquake.  I  have  seen  a  number 
of  cases  recently  in  which  the  emotional  element 
was  unfortunately  prominent.  One  case  in  par- 
ticular originated  from  the  shock  of  an  insignificant 
fall  of  a  foot  or  two.  Another  was  aggravated  by 
family  troubles,  while  a  third  one,  progressing 
nicely  under  my  routine  treatment,  was  set  back 
abruptly  and  the  pulse  bounded  up  40  beats  a  min- 
ute because  of  the  excitement  accompanying  a  sud- 
den sickness  of  another  member  of  the  family. 

Unfortunately,  the  control  of  the  mental  and 
psychic  influences  is  most  difficult;  nevertheless,  it 
is  of  highest  importance  to  attempt  as  best  one  may 
the  removal  of  the  sources  of  psychic  irritation — 
fear  and  worry,  and,  be  it  remarked,  much  "com- 
pany" and  exciting  reading. 

Practically  all  subjects  of  hyperthyroidism  are 
poorly  nourished,  despite  the  fact  that  they  may  be 
hearty  eaters  and  their  digestion  may  seem  to  be 
perfectly  normal.  The  reason  for  this  is,  of  course, 
that  the  thyroid  gland  controls  cell  nutrition  and 
the  excessive  stimuli  coming  from  this  gland,  as 
the  result  of  its  disordered  function,  cause  the  foods 
to  be  burnt  up  too  rapidly;  malnutrition  and  even 
emaciation,  hence,  being  the  rule. 

For  this  reason,  the  dietary  must  be  generous 
and  fattening.  In  addition  to  three  liberal  meals 
containing  as  few  purin-bearing  articles  as  possible, 


192  THE  INTERNAL  SECRETIONS 

I  am  in  the  habit  of  prescribing  buttermilk  pre- 
pared with  a  reliable  culture  of  the  bulgaric  bacillus 
and  to  be  drank  at  least  twice  a  day,  conveniently 
fitted  in  between  the  meals;  and  crackers  with  the 
buttermilk,  if  the  patient  cares  for  them.  I  am  also 
partial  to  ice-cream  as  a  daily  adjuvant  to  the  diet- 
ary, not  merely  because  of  the  gustatory  pleasure 
it  affords,  but  because  of  its  high  caloric  value. 

Another  article  of  the  diet  suggested — one  pos- 
sibly not  possessed  of  any  well-defined  nourishing 
value,  but  which  is  of  undoubted  service,  not  alone 
in  this  disease,  but  in  many  nutritional  disorders, 
is  a  rich  vegetable  consomme  prepared  by  cooking 
together  various  and  differing  combinations  of  veg- 
etables, especially  the  green  stuffs.  In  these,  I  in- 
clude: spinach,  beet  tops,  turnip  tops,  celery  (in- 
cluding the  leaves),  celeriac,  asparagus  (not  in  ev- 
ery case,  because  of  the  renal  stimulant  present), 
tomatoes,  fresh  young  peas  (with  pods  included), 
stringbeans,  turnips,  potatoes,  in  fact,  almost  any 
vegetable,  boiling  them  in  sufficient  water  for  a 
long  enough  time  completely  to  extract  the  saline 
elements,  so  that  they  may  serve  as  an  efficient 
nutrient  instead  of  being  thrown  away,  as  is  the 
rule  in  our  present  wretched  cookery.  Needless  to 
repeat  here  that  these  vegetable  salts  are  of  real 
value  in  many  disorders  of  metabolism,  and,  surely, 
it  is  correct  to  put  hyperthyroidism  in  this  cate- 
gory. Incidentally,  the  cook  can  modify  the  flavor 
and  color  of  the  consomme  and  change  its  concen- 


t 

IN  PRACTICAL  MEDICINE  193 

tration  at  will;  the  form  of  serving  may  vary  from 
a  hot  cup  to  jelly  (made  with  pure  gelatin)  ;  it  may 
be  given  iced  or  frozen;  also,  it  makes  a  very  pal- 
atable dietetic  adjuvant  in  many  conditions. 

Not  infrequently  the  oral  administration  of  pan- 
creatin  may  prove  of  distinct  advantage,  and  I 
sometimes  think  that  it  has  a  dual  action,  in  not 
merely  increasing  the  digestion  and,  hence,  favor- 
ing the  assimilation  of  more  much-needed  food,  but 
also  acting  upon  the  sympatheticotonic  condition 
characteristic  of  this  malady. 

A  word  of  explanation  may  here  be  in  order. 
Toxemia  having  its  origin  in  the  thyroid  gland  or 
from  any  other  cause,  including  the  emotional  stim- 
uli referred  to,  gives  rise  to  hyperadrenia;  in  fact, 
hyperthyroidism  nearly  always  is  accompanied  by 
hyperadrenia,  as  may  be  quickly  demonstrated  by 
the  application  of  Loewi's  instillation  test  (put- 
ting one  drop  of  adrenalin  solution  into  the  con- 
junctival sac  and  observing  its  influence  upon  pupil- 
lary action).*  The  dry  mouth,  the  tremor,  and  some 


♦Quoting  from  W.  M.  Barton's  excellent  little  "Manual  of 
Vital  Function  Testing  Methods  and  their  Interpretation"  (Bos- 
ton, Richard  G.  Badger):  "In  1908  Loewi  made  the  observa- 
tion that  after  removal  of  the  pancreas  in  certain  animals,  the 
installation  of  adrenalin  into  the  eye  will  cause  dilatation  of  the 
pupil.  Loewi  attributed  the  mydriasis  to  increased  excitability 
of  the  sympathetic  system  brought  about  by  the  removal  of  the 
inhibitory  effect  of  the  pancreatic  internal   secretion." 

This  has  been  used  successfully  in  diabetes  mellitus,  but  it 
will  also  be  positive  in  Graves'  disease  due  to  the  increased 
sympatheticotonus.  Hence  it  is  valuable  in  both  these  condi- 
tions, the  reaction  in  the  former  being  due  to  a  deficiency 
brought  about  by  the  lack  of  the  pancreatic  hormone  and  in  the 
latter  to  an  excess  of  the  chromaffin  hormone  (the  mutual  an- 
tagonist to  the  pancreatic  hormone). 


194  THE  INTERNAL  SECRETIONS 

of  the  other  nervous  manifestations  seem  to  me  to 
be  as  much  of  adrenal  as  of  thyroid  origin.  Now,  it 
happens  that  the  internal  secretion  of  the  pancreas 
exerts  a  decided  antagonistic  action  upon  that  of 
chromaffin  cells,  and,  in  fact,  it  has  by  some  been 
called  the  "pancreatic  anti-hormone";  hence,  any 
means  of  facilitating  this  function  of  the  pancreas 
(in  addition  to  its  external  secretory  powers)  is 
distinctly  in  order. 

The  administration  of  pancreatin  not  merely  as- 
sists in  digesting  certain  foodstuffs  in  the  bowels, 
but,  like  all  organotherapeutic  measures,  brings 
about  a  homostimulant  action  or,  in  other  words, 
it  favors  the  work  of  the  pancreas,  increasing  the 
output  of  its  chemical  substances.  Within  the  past 
year,  several  communications  regarding  the  use  of 
pancreatin  in  hyperthyroidism  have  appeared  in 
print,  and,  as  for  myself,  while  I  do  not  think  of 
making  it  the  main  treatment,  I  consider  that  15 
to  30  grains  or  more  per  day,  given  after  meals, 
certainly  makes  a  useful  adjuvant. 

All  the  above  seems  to  be  of  practical  value,  while 
I  have  purposely  refrained  from  commenting  upon 
the  fairly  well-known  drug-treatment  and  the  con- 
sideration of  the  need  for  surgery  and  Watson's 
excellent  quinine-urea  injection-method,  all  of 
which  are  the  subjects  of  recent  communications. 

I  cannot  refrain,  however,  from  recommending 
the  method  of  treatment  suggested  last  year  by  Dr. 
George  Richter,  of  St.  Louis,  which  consists  in  the 


IN  PRACTICAL  MEDICINE  195 

daily  administering  from  15  to  30  grains  of  the 
desiccated  anterior  lobe  of  the  pituitary  body.  I 
have  adopted  this  treatment  in  the  case  of  11  pa- 
tients, some  of  them  ambulatory  and  others  rest- 
ing in  bed,  and  am  convinced  that  there  is  brought 
about  a  valuable  sedative  action  that  is  of  distinct 
advantage,  and  I  am  hoping  to  be  able  some  day  to 
say  definitely  that  this  endocrine  organ  is  the  rem- 
edy for  hyperthyroidism.  At  present,  I  can  recom- 
mend it  as  a  very  useful  adjunct  to  the  other  treat- 
ment above  outlined,  which  has  become  a  routine 
in  my  hands  because  of  its  effectiveness  and  rea- 
sonableness. 


XVI 

THE   MAMMA  AS  AN   INTERNAL   SECRE- 
TORY ORGAN:  MAMMARY 
THERAPEUTICS 

IT  is  surprising  how  many  of  the  glandular 
structures  of  the  body  whose  secretory  activities 
are  so  well  known  are  beginning  to  be  classed  as 
having  an  additional  and  equally  important  func- 
tion, i.  e.,  that  of  internal  secretion.  It  now  seems 
beyond  question  that  in  addition  to  the  pancreas, 
liver  and  gonads,  the  mammary  glands  also  must 
be  classed  among  the  organs  with  a  dual  function, 
that  of  the  production  of  both  internal  and  external 
secretions.  Incidentally,  there  seems  to  be  some 
basis  for  the  belief  that  the  parotid  is  another  of 
the  glands  with  ducts  which  must  be  considered  as 
having  an  internal  secretion  as  well  as  an  external 
secretion. 

The  fundamentals  which  serve  as  the  basis  of 
this  paper  may  be  summarized  in  the  following 
postulates:  (1)  The  mammae,  in  addition  to  their 
galactogenic  function,  produce  an  internal  secre- 
tion, are  themselves  subject  to  hormone  influences, 
and  hence  must  be  considered  as  part  of  the  en- 
docrine system.  (2)  Suitably  prepared  extracts  of 
the  mammary  parenchyma  contain  a  principle  (pre- 
sumably a  hormone)  which  exerts  a  definite  physi- 


Reprinted  from  The  Woman's  Medical  Journal  (Cincinnati), 
March,  1915 

(196) 


IN  PRACTICAL  MEDICINE  197 

ologic  action,  and  hence  have  inherent  possibilities 
of  therapeutic  utility. 

There  are  quite  a  number  of  reports  of  experi- 
ments made  in  different  parts  of  the  world  which 
give  abundant  evidence  of  the  truth  of  the  first  pos- 
tulate, a  limited  number  of  which  will  be  referred 
to  briefly  here.  It  is  convenient  first  to  consider 
the  hormone  control  of  the  mamma  and  later  to 
mention  its  hormone  influence  upon  other  organs 
and  functions. 

In  1906,  in  the  Institute  of  Physiology,  Uni- 
versity College,  London,  Starling*  and  his  associ- 
ate, Miss  Lane-Claypon,  demonstrated  that  the 
fetus  is  the  seat  of  the  production  of  a  hormone 
which,  passing  through  the  placental  circulation  to 
the  mother,  brings  about  a  specific  stimulation  of 
the  mammary  glands,  first  to  enlarge  and  later  to 
perform  their  milk-producing  function.  This  sub 
stance  seems  to  be  of  a  definite  chemical  nature, 
and  may  even  be  obtained  from  dried  embryo  sub- 
stance, from  which  it  is  extracted  in  a  manner 
somewhat  similar  to  the  production  of  secretin  from 
the  mucosa  of  the  duodenal  walls. 

One  of  the  most  remarkable  of  all  their  experi- 
ments was  the  establishment  of  lactation  in  virgin 


*A  pioneer  in  the  study  of~T:he  hormones,  the  discoverer  of 
the  "original  hormone"  secretin,  and  the  originator  of  the  term 
"hormone"  (Gr.,  I  arouse,  excite  or  set  in  motion).  Quite  a 
full  consideration  of  the  history  and  importance  of  Starling's 
work  with  secretin,  as  well  as  of  the  importance  of  the  discovery, 
production  and  action  of  hormones  and  the  fundamental  prin- 
ciples of  hormone  therapy  will  be  found  in  my  recent  work, 
"Practical  Hormone  Therapy." 


198  THE  INTERNAL  SECRETIONS 

rabbits  by  the  injection  of  these  extracts.  Several 
other  investigators  since  have  confirmed  this  work, 
and,  in  addition,  have  shown  that  fetal  extracts 
from  one  animal  will  be  active  in  bringing  about 
this  definite  physiologic  action  in  animals  of  a  dif- 
ferent species.  So  far  as  I  am  aware,  no  use  has 
been  made  of  this  in  medicine,  for  obvious  reasons. 
Be  that  as  it  may,  this  was  an  important  revelation, 
although  it  was  by  no  means  the  original  work 
which  showed  that  the  mammary  gland  was  influ- 
enced by  the  chemical  messengers.  The  experi- 
ments of  Ribbert,  made  in  the  late  nineties,  seem  to 
be  the  first  in  this  line,  and  while  they  did  not  quite 
reveal  the  character  of  the  stimuli,  they  undoubt- 
edly proved  that  the  development  of  the  mammary 
gland  was  not  solely  under  the  nervous  control. 
Ribbert  and  his  associates  transplanted  a  portion 
of  the  mamma  from  a  virgin  rabbit  into  a  pregnant 
animal,  and  in  due  time  the  graft  developed  and 
actually  secreted  milk. 

The  fetal  hormone  or,  as  it  was  originally  termed, 
the  "mamma  hormone,"*  is  not  the  only  chemical 


*The  term  "mamma  hormone"  is  fortunately  becoming  rare, 
since,  as  will  be  seen  later,  this  term  properly  designates  the 
hormone  produced  in  the  mammae — not  the  hormone  which 
activates  them.  Incidentally,  it  will  be  remembered  by  those 
acquainted  with  the  remarkable  results  of  the  work  done  with 
secretin,  that  it  was  originally  called  "pancreatic  secretin,"  not 
because  it  is  produced  by  the  pancreas,  but  because  it  activates 
it.  It  is  now  called  "duodenal  secretin,"  because  it  is  produced 
in  the  duodenal  walls,  though,  of  course,  it  still  remains  the 
principal  activator  of  the  pancreatic  glands.  The  later  nomen- 
clature makes  it  possible  to  differentiate  between  secretins  from 
varying  sources,  as,  for  instance,  the  gastric  or  pyloric  mucosa. 


IN  PRACTICAL  MEDICINE  199 

messenger  concerned  in  the  control  of  the  mam- 
mae, for  it  is  evident  that  other  hormone  factors 
are  concerned  in  the  development  and  establish- 
ment of  mammary  activity.  There  is  a  very  inti- 
mate relationship  between  the  ovaries  and  the 
mammae,  which  has  been  demonstrated  by  Bouin 
and  Ancel.  These  investigators  found  that  by  arti- 
ficially rupturing  the  luteal  follicles  of  the  ovaries 
of  rabbits,  in  addition  to  causing  the  discharge  of 
the  ovum  there  was  produced  a  chemical  substance 
— a  hormone — which  causes  a  marked  histological 
change  in  the  mammary  gland,  quite  apart  from 
the  presence  of  the  products  of  conception  in  the 
uterus  (for  the  rabbit  was  not  pregnant).  In  con- 
sidering the  reports  of  these  remarkable  experi- 
ments, an  editorial  writer  in  the  Journal  of  the 
American  Medical  Association  states  that  "these 
facts  serve  to  lend  new  emphasis  to  the  dependence 
of  such  physiologic  response  as  mammary  develop- 
ment on  other  than  purely  nervous  relations.  Thev 
add  to  the  coming  significance  of  hormone  activi- 
ties in  the  interdependence  of  various  parts  of  the 
organism." 

It  is  a  well-known  fact  that  experimental,  as  well 
as  clinical,  ovariotomy  frequently  is  followed  by 
retrogressive  changes  in  the  breasts  and  even  by 
their  disappearance,  while  experiments  on  animals 
have  shown  that  under  such  circumstances  an 
ovarian  graft  will  bring  about  a  re-establishment  of 
the  growth  and  activity  of  these  organs.     There 


200  THE  INTERNAL  SECRETIONS 

seems  to  be  conclusive  proof  that  the  internal  se- 
cretion of  the  ovary  is  a  factor  which  controls  or  at 
least  influences  mammary  activity. 

The  study  of  mammary  development  may  be 
quickly  broadened  into  a  study  of  the  hormone  in- 
fluences which  control  these  organs,  and  a  very 
complete  consideration  of  this  subject  forms  the 
These  de  Doctorate  of  Schil  (1912).  A  resume  of 
Schil's  work  will  be  found  in  my  book,  "Practical 
Hormone  Therapy,"  and  I  can  do  no  better  than  to 
include  a  part  of  it  here: 

Schil  recognizes  six  stages  in  the  evolution  of 
the  mammae:  (1)  The  stage  of  development,  di- 
vided into  an  organogenetic  phase  and  a  phase  in 
which  there  is  secretory  activity  (the  lactation  of 
the  new-born).  This  secretory  phase  is  dependent 
upon  a  hormone  passing  from  mother  to  fetus 
through  the  placenta.  This  same  hormone  activates 
mammary  secretion  in  the  mother.  (2)  The  pre- 
pubertal stage,  which  lasts  until  puberty  (or  the 
first  rut  in  animals),  during  which  the  glands  are 
functionally  inactive.  (3)  The  stage  of  puberty, 
characterized  by  a  considerable  increase  in  the 
glandular  parenchyma.  This  growth  is  dependent 
upon  the  exciting  influence  (by  means  of  a  hor- 
mone) of  the  mature  Graafian  follicles  in  animals, 
in  which  non-spontaneous  ovulation  is  produced 
artificially,  and  in  the  case  of  spontaneous  ovula- 
tion, to  the  follicles  and  corpora  lutea,  which  de- 
velop from  these  follicles  after  dehiscence.   (4)  The 


IN  PRACTICAL  MEDICINE  201 

gravid  stage,  which  is  divided  into  two  phases:  a, 
Growth,  especially  evident  during  the  early  part 
of  gestation,  as  a  result  of  which  the  glands  attain 
their  complete  development;  and,  b,  a  so-called 
"phase  glandulaire  gravidique,"  which  follows  the 
completion  of  growth  and  is  characterized  by  se- 
cretory activity,  the  product  of  which  is  known  as 
the  "colostrum."  Each  of  these  two  phases  is  the 
result  of  hormone  action,  the  first  due  to  a  kineto- 
genic  hormone  from  the  corpus  luteum  of  preg- 
nancy, and  the  second  to  a  criticogenic  hormone, 
which  seems  to  come  from  a  secretory  portion  of 
the  placenta  during  the  second  part  of  gestation, 
or  from  a  myometrial  gland.  (5)  A  post-partum 
stage,  continuing  during  lactation  until  the  glands 
are  again  in  repose,  and  divided  into  two  phases: 
a,  Post-partum  glandular  activity,  in  which  the 
milk  is  produced;  and  b,  the  phase  of  post-partum 
retrogression,  in  which  galactogenesia  ceases,  and 
the  parenchyma  is  slightly  diminished.  Of  these 
two  phases  only  the  first  is  of  interest,  since  the 
second  is  caused  by  the  absence  of  stimuli.  The 
milk,  released  during  pregnancy  by  an  endogenous 
stimulus,  is  maintained  by  an  exogenous  stimulus, 
the  act  of  suction.  (6)  A  senile  stage,  associated 
with  involution,  and  corresponding  to  the  period  of 
cessation  of  genital  activity. 

There  is,  of  course,  further  proof  of  the  intimate 
relationship  between  the  mammae  and  ovaries,  as 
for  example,  the  well  established  fact  that  the  oper- 


202  THE  INTERNAL  SECRETIONS 

ation  of  spaying  dairy  cows  at  the  time  of  giving 
their  greatest  flow  of  milk  has  an  influence  upon 
the  lacteal  period.  In  a  personal  communication 
from  the  Bureau  of  Animal  Industry  the  following 
appears:  "It  is  a  well  established  fact  that  in 
spayed  dairy  cows  the  period  of  lactation  is  pro- 
longed." 

Additional  emphasis  is  lent  by  the  fact  that  the 
function  of  ovulation  is  retarded  and  sometimes 
entirely  stopped  during  prolonged  lactation,  pre- 
sumably because  in  the  stage  of  mammary  activity 
the  increased  elaboration  of  the  internal  secretion 
antagonizes  ovarian  activity  in  a  greater  or  less  de- 
gree. It  is  well  known  that  pregnant  cows  as  a 
rule  show  a  tendency  to  lessen  the  supply  of  their 
milk  after  conception  takes  place. 

In  a  conversation  on  this  subject  the  other  day, 
it  was  stated  that  quite  frequently  women  with 
large  mammary  development  menstruate  scantily, 
while  those  with  small  breasts  not  infrequently  are 
subject  to  menorrhagia.  This  is  by  no  means  al- 
ways the  case,  but  it  points  at  least  to  an  antago- 
nism between  the  mammae  and  the  ovaries. 

As  still  further  incontrovertible  evidence  of  the 
hormone  control  of  galactogenesia  I  will  cite  the 
remarkable  experience  of  the  famous  Blazek  twins. 
It  may  be  remembered  that  this  pair  of  pyopagous 
female  twins  matured  and  one  of  them  married.  In 
due  time  she  became  pregnant  and  was  success- 
fully confined  and  after  delivery  the  secretion  of 


IN  PRACTICAL  MEDICINE  203 

milk  also  took  place  in  the  non-puerperal  sister.  In 
other  words,  both  were  able  to  nurse  the  infant, 
and  obviously  the  influences  which  stimulated 
mammary  activity  in  the  unmarried  sister  were  of 
a  hormone  nature. 

Most  of  these  facts,  it  is  true,  indicate  that  the 
mammae  are  subject  to  hormone  influences — i.  e., 
are  controlled  in  part  by  an  internal  secretion  of 
the  ovary,  or  other  glands;  but  if  the  second  pos- 
tulate is  considered,  satisfactory  proof  of  the  in- 
ternal secretory  activity  of  the  mammae  will  be 
forthcoming,  for,  as  will  shortly  be  seen,  the  an- 
tagonistic relation  between  the  mammae  and  the 
ovaries  is  made  good  use  of  as  the  basis  of  certain 
therapeutic  procedures. 

A  consideration  of  several  of  the  numerous  ref- 
erences to  the  use  of  extracts  of  the  parenchyma 
of  mammary  glands  as  a  therapeutic  agent  seems  to 
show  conclusively  that  they  possess  a  decided 
therapeutic  influence  and  at  the  same  time  empha- 
sizes the  importance  of  what  must  still  be  called  a 
much  neglected  field  of  therapeutics.  As  a  matter 
of  fact  I  am  sure  that  "hormone  therapy,"  as  I 
like  to  call  it,  is  neither  studied  nor  practiced  as 
much  as  it  deserves;  and  those  who  will  take  the 
time  to  investigate  the  scientific  use  of  organo- 
therapeutic  extracts  will  quickly  find  that  the  as- 
tonishing results  accredited  to  thyroid,  adrenal  or 
pituitary  medication  are  by  no  means  limited  to 
these  few;  but  that  a  vast  territory  will  be  opened 


204  THE  INTERNAL  SECRETIONS 

up  in  which  will  be  found  many  proved  and,  later, 
more  as  yet  unproved,  means  which  will  facilitate 
the  solution  of  many  a  therapeutic  puzzle. 

Mammary  extract  is  produced  from  the  care- 
fully dissected  parenchyma  of  the  udders  of  cows, 
goats  or  ewes,  and  is  prepared  with  the  precautions 
customary  in  the  manufacture  of  effective  organo- 
therapeutic  extracts.  It  is  obtainable  in  dry  form 
or  in  solution  (in  ampules).  Injections  of  the  lat- 
ter seem  to  be  somewhat  painful  and,  so  far  as  I 
can  see,  have  no  special  advantage  over  the  powder 
or  tablets  given  by  mouth,  as  in  many  cases  the 
results  are  just  as  evident  following  treatment  by 
the  internal  as  by  the  hypodermic  or  intramuscu- 
lar method,  tending  to  prove  that  whatever  the 
principle  may  be  that  is  the  cause  of  the  therapeutic 
activity  of  this  extract,  it  is  not  destroyed  when 
passing  through  the  stomach. 

As  we  have  already  seen,  there  is  a  decided  an- 
tagonism between  the  mammae  and  the  ovaries, 
and  this  fact  is  the  basis  for  the  principal  use  of 
mammary  extract.  It  is  used  to  overcome  the  re- 
sults of  excessive  ovarian  activity.  Among  the 
conditions,  which  have  been  classed  under  this  head 
are  menorrhagia  with  increased  uterine  congestion, 
uterine  hypertrophy  and  fibroid  degeneration,  as 
well  as  certain  conditions  in  which  there  is  an  in- 
creased degree  of  ovarian  activity.  The  chief 
every-day  indications  for  mammary  therapy  are 
functional  uterine  hemorrhages  and  fibroids. 


IN  PRACTICAL  MEDICINE  205 

A  number  of  investigators  have  used  this  method 
to  produce  uterine  depletion  and  to  control  hemor- 
rhages shown  to  be  due  to  functional  causes  as 
distinguished  from  those  of  organic  origin,  such 
as  the  presence  of  foreign  bodies  in  the  uterus, 
polypi,  placental  remains,  cancer,  etc.  Clearly 
medicinal  therapy  is  not  likely  to  be  very  effective 
in  such  conditions  as  these  latter,  where  the  re- 
moval of  the  foreign  body  or  growth  is  the  most 
reasonable  procedure.  However,  mammary  extract 
has  been  used  in  the  post-operative  treatment  of 
such  cases,  especially  when  there  has  been  a  ten- 
dency to  protracted  oozing. 

Pochon  has  used  mammary  substance  and  re- 
commends it  for  its  decided  anti-hemorrhagic  in- 
fluence (however,  it  is  not  a  styptic  by  any  means) 
and  calls  attention  to  the  fact  that  while  mammary 
extract  tends  to  cause  uterine  depletion,  ovarian 
extracts  have  an  entirely  opposite  tendency,  caus- 
ing an  increased  uterine  blood  supply. 

Luncz,  in  his  interesting  monograph,  has  gath- 
ered a  number  of  reports  of  benign  cases  in  which 
mammary  opotherapy  caused  an  entire  cessation  of 
uterine  hemorhrage  in  persons  of  widely  varying 
age. 

Other  writers  have  gone  further,  among  them 
Forgue  and  Massabuan,  who  besides  demonstrat- 
ing clinically  the  anti-hemorrhagic  action  of  this 
preparation,  have  shown  experimentally  that  at 
the  menopause  there  frequently  is  an  obvious  in- 


206  THE  INTERNAL  SECRETIONS 

crease  in  the  corpora  lutea  with  hypertrophy  of 
these  cells.  They  presume  that  the  hemorrhages 
so  common  at  this  time  may  be  due  to  two  causes: 
Temporary  increased  production  of  the  luteal 
hormone,  and  an  associated  decrease  in  the  pro- 
duction of  its  antagonist — the  mammary  hormone 
— resulting,  of  course,  from  the  usual  retrogressive 
changes  expected  in  the  mammae  at  this  period. 
This  harmonizes  entirely  with  the  facts  previously 
collated  here,  and  is  further  evidence  of  the  sound- 
ness of  the  position  of  this  form  of  treatment  in 
such  cases. 

There  are  numerous  reports  showing  the  anti- 
hemorrhagic  influence  of  mammary  substance.  I 
have  personally  prescribed  and  recommended  it  in 
a  number  of  cases  with  good  results.  Battuaud 
indicates  that  this  form  of  medication  has  proved 
valuable  in  the  control  of  menorrhagia  in  young 
girls,  just  as  it  has  been  found  serviceable  in  met- 
rorrhagia of  the  climacteric.  Congestive  conditions 
of  the  ovary  resulting  from  inflammation  of  the 
adnexa  and  other  causes  may  be  reduced  in  this 
manner,  although,  of  course,  the  influence  is  more 
mechanical — i.  e.,  decongestion  is  brought  about 
in  a  chemical  way  and  there  is  no  particular  action 
on  the  infective  process.  In  other  words,  mammary 
extract  is  a  valuable  adjunct  to  the  specific  anti- 
infection  treatment,  which  is  now  generally  recog- 
nized to  be  the  bacterin  method. 

Dalche,  Jayle,  Pozzi  and  other  French  gynecolo- 


IN  PRACTICAL  MEDICINE  207 

gists  are  convinced  of  the  efficacy  of  this  method, 
while  virtually  all  the  references  to  mammary  ther- 
apy in  American  medical  literature  are  quite  a  num- 
ber of  years  old,  the  chief  papers  being  those  of 
Pryor,  Crouse  and  Shober. 

The  original  application  of  mammary  therapy 
seems  to  have  been  made  by  Robert  Bell,  of  Glas- 
gow, in  1896,  and  his  initial  experiences  were  in  the 
treatment  of  uterine  fibroids.  He  reported  before 
the  British  Gynecological  Society  four  cases,  two 
of  which  were  suffering  from  fibroids,  the  first  in 
a  woman  of  forty-eight,  the  large  fibrous  tumor 
being  reduced  75  per  cent,  after  four  months'  treat- 
ment, the  menstrual  troubles  having  in  the  mean- 
time completely  disappeared.  In  the  second  case 
a  smaller  fibroma  was  much  reduced  in  size  after 
three  months'  treatment,  the  hemorrhage  having 
been  stopped  and  the  anemia  controlled. 

In  the  last  18  years  there  have  been,  perhaps,  180 
cases  reported  in  the  literature,  the  majority  of 
them  in  Russia,  although  quite  a  number  will  be 
found  in  the  French  journals.  Feodoroff,  Professor 
in  the  University  at  Petrograd,  has  made  several 
communications  on  this  subject  and  in  his  most  re- 
cent statistical  report  refers  to  a  series  of  43  women 
treated  for  fibroids,  in-25  of  whom  the  uterus  had 
attained  the  approximate  size  of  the  gravid  uterus 
at  two  or  three  months,  in  16  others  the  tumor  be- 
ing larger  and  corresponding  to  the  gravid  uterus 
at  four  to  six  months,  while  in  two  of  them  the 


208  THE  INTERNAL  SECRETIONS 

tumor  extended  beyond  the  umbilicus.  One-third 
of  all  these  cases  was  completely  cured;  in  53  per 
cent,  there  was  a  decided  reduction  in  the  volume 
of  the  tumor;  in  over  80  per  cent,  the  hemorrhage 
was  completely  stopped,  and  in  47  per  cent,  the 
pain  commonly  noted  was  relieved.  In  only  14  per 
cent,  of  this  series  was  no  result  whatever  secured. 
It  is  only  fair  to  add  that  one-half  of  the  complete 
cures  were  secured  in  the  first  series  (those  in 
whom  the  volume  of  the  uterus  corresponded  to  the 
pregnant  uterus  at  two  or  three  months)  and  that 
in  the  two  extraordinarily  large  tumors  no  result 
was  obtained.  These  figures,  apart  from  the  re- 
ports of  several  other  writers,  would  almost  seem 
to  be  convincing  evidence  of  the  value  of  mam- 
mary substance  in  therapeutics,  for  despite  the  fact 
that  FeodorofFs  name  is  strange  in  this  country,  he 
is  a  very  well  known  gynecologist  in  Russia. 

Another  Russian  investigator,  Mekerttschiantz, 
is  more  enthusiastic  in  his  praise  of  this  method, 
and  goes  so  far  as  to  call  mammary  extract  "the 
touchstone  for  all  cases  of  uterine  fibroids";  and 
rightly  suggests  that  it  be  given  a  thorough  trial 
for  several  months  before  operative  measures  are 
decided  upon.  (This,  at  least,  is  a  fair  presump- 
tion, for,  in  my  opinion,  the  surgeon  is  not  always 
justified  in  performing  hysterectomy  or  pan-hys- 
terectomy until  every  reasonable  medical  proced- 
ure has  been  thoroughly  tried  without  avail.)  He 
calls  attention  to  the  fact  that  uterine  contractions 


IN  PRACTICAL  MEDICINE  209 

may  be  caused  by  this  method,  and  also  believes 
that  the  retrogressive  changes  that  are  brought 
about  in  interstitial  fibroids  are  due  to  their  trans- 
formation into  subserous  fibroids  which  later  be- 
come pediculated  and  are  either  cast  off  or  ab- 
sorbed. 

In  all  of  his  SO  or  more  cases,  Mekerttschiantz 
secured  benefit,  the  hemorrhage  was  controlled  in 
all,  the  tumor  reduced  to  a  minimum  in  two-thirds, 
and  a  noticeable  betterment  in  general  health  was 
remarked.  It  is  interesting  to  note  that  in  cases 
of  fibroid  complicated  with  pregnancy,  mammary 
therapy  exercises  a  maximum  influence  on  the  ret- 
rogression of  the  tumor,  because  the  effect  of  the 
extract  is  amplified  by  the  increasd  mammary  ac- 
tivity resulting  from  the  normal  physiologic  stim- 
uli, as  well  as  by  the  homostimulation*  which  is 
also  brought  about. 

Naturally  in  all  organic  diseases  the  possibilities 
for  success  in  therapeutics  are  considerably  less 
than  in  functional  disorders,  hence  it  must  not  be 
expected  that  the  application  of  this  method  of 
treating  fibroids  is  going  to  be  nearly  as  effective 
as  in  the  treatment  of  the  less  serious  and  more 
easily  controlled  functional  disorders.  In  other 
words,  functional  menorrhagia  responds  to  mam- 
mary therapy  much  more  readily  than  do  uterine 


♦"Homostimulation"  is  a  term  coined  by  Hallion  of  Paris 
to  designate  a  uniform  property  of  organotherapeutic  extracts 
which  is  summarized  in  what  is  now  called  "Hallion's  Law"  (See 
page  3.) 


210  THE  INTERNAL  SECRETIONS 

fibroids;  and  in  the  treatment  of  the  latter  the 
hemorrhage  and  other  symptoms  likely  will  be  in- 
fluenced more  and  earlier  than  the  tumor  itself. 

While  the  use  of  mammary  extract  in  therapeu- 
tics has  not  yet  reached  the  same  unassailable  posi- 
tion that  has  been  attained  by  certain  other  glandu 
lar  extracts,  notably  thyroid,  pituitary  and  adrenal, 
it  is  none  the  less  a  useful  procedure  for  the  gyne- 
cologist and  the  general  practitioner;  and  while  the 
experiences  outlined  previously  may  not  be  always 
duplicated  in  their  entirety,  there  can  be  no  doubt 
that  it  is  an  effective  method  and  that  it  deserves, 
like  many  other  phases  of  practical  hormone  ther- 
apy, more  fully  outlined  in  my  book  of  that  name, 
to  be  raised  from  the  obscurity  in  which  it  is  at 
present  involved. 

It  is  not  as  difficult  to  secure  effective  mammary 
preparations  as  has  been  hinted  by  many  with 
whom  I  have  spoken  or  corresponded.  In  every 
country  that  I  have  visited  I  have  been  able  to  find 
useful  preparations  and  no  harm  can  come  from 
referring  to  some  of  these.  In  England  one  can 
quickly  secure  Mamos  (B.,  W.  &  Co.),  Ovomam- 
moid  Comp.  and  the  Russian  product,  Mamminum. 
In  France  there  are  at  least  12  "extraits  mam 
maires,"  those  of  Carrion,  Choay  and  Chaix  of 
Paris  ranking  among  the  best.  In  this  country  one 
can  usually  secure  the  products  named  above,  as 
well  as  Mammary  Substance  (Armour  &  Co.)  and 
Mammogen  (G.  W.  Carnrick  Co.),  and  most  of  my 


IN  PRACTICAL  MEDICINE  211 

more  recent  personal  experiences  have  been  lim- 
ited to  these  latter. 

Before  closing,  a  few  words  may  be  said  regard- 
ing dosage.  It  is  usually  advisable  to  give  5  or  6 
grains  t.  i.  d.  Larger  doses  may  be  given,  as  much 
as  15  or  20  grains  at  a  dose.  (Attention  is  called 
to  the  fact  that  not  every  tablet  contains  the  amount 
of  actual  substance  that  corresponds  to  the  weight 
of  the  tablet,  the  amount  varying  with  the  products 
of  different  manufacturers.)  It  seems  best  to  give 
mammary  extract  just  before  meals,  for  in  occa- 
sional cases  there  is  a  slight  tendency  to  digestive 
derangement  following  its  use.  In  fact,  rarely  a 
case  will  be  found  in  which  it  is  necessary  to  dis- 
continue the  use  of  this  preparation  and  to  re-estab- 
lish the  dosage  in  very  gradual  steps,  commencing 
with  one  or  two  grains  a  day  and  increasing  as 
rapidly  as  is  consistent  with  the  circumstances. 

Obviously  in  the  treatment  of  conditions  of  long 
standing  this  method  must  be  continued  over  a 
long  period,  and  Battuaud  in  recommending  0.5 
Gram  (7y2  grains)  of  the  active  substance  twice 
a  day,  suggests  that  when  attempting  to  control 
hemorhrage  between  the  periods  the  above  dose 
should  be  continued  daily  and  doubled  during  the 
hemorrhage.  It  has  been  suggested  that  mammary 
extract  should  not  be  given  during  the  menses,  but 
I  have  not  found  this  so.  After  all,  each  patient  is 
a  law  unto  herself,  and,  as  with  many  other  thera- 
peutic procedures,  the  best  dose  is  "enough." 


XVII 

CONNECTING    LINKS    BETWEEN    ENDO- 
CRINOLOGY AND  OTO-RHINOLOGY 

ON  first  thought  the  connection  between  the  in- 
ternal secretory  organs  and  the  ear,  nose  and 
throat  is  not  particularly  intimate  and,  perhaps, 
some  of  you  have  felt  that  the  hour  this  evening 
might  be  ill-spent  in  listening  to  what  I  have  to 
say.  If  so,  I  hope  that  you  may  be  pleasantly  dis- 
appointed, for  I  believe  that  the  connection  be- 
tween these  two  branches  of  medicine  is  just  as 
evident  and  as  important  as  those  well-defined 
links  between  other  systems  or  organs  of  the  body 
which  have  become  better  known  as  our  knowledge 
of  the  hormones  has  increased. 

For  the  sake  of  convenience  I  have  divided  my 
remarks  into  two  parts,  in  the  first  of  which  I  hope 
to  show  that  a  well-marked  and  fundamental  rela- 
tionship exists  between  certain  of  the  glands  of  in- 
ternal secretion  and  some  of  the  disorders  in  your 
special  field  and  vice  versa;  and  in  the  second, 
briefly  to  consider  several  profitable  phases  of  or- 
ganotherapy which  specialists  such  as  yourselves 
may  apply  quite  frequently. 

Naturally  the  thyroid  gland  would  be  the  first 
to  engage  our  attention,  for  it  is  among  the  most 

An  address  read  before  the  Eye,  Ear,  Nose  and  Throat  Sec- 
tion, Los  Angeles  County  Medical  Association,  May  1,  1916,  and 
published  in  The  Laryngoscope  (St.  Louis),  August,  1916. 

(212) 


IN  PRACTICAL  MEDICINE  213 

important  of  the  hormone-bearing  organs.  The 
thyroid  gland  exerts  the  same  influence  upon  the 
control  of  the  metabolism  in  the  cells  of  the  struc- 
tures constituting  your  province  of  medicine,  as  it 
does  in  the  maintenance  of  cell  nutrition  and  de- 
toxication  in  any  other  part  of  the  body.  The  great 
principle  involved  in  the  relation  of  thyroid  insuffi- 
ciency and  the  condition  of  cellular  infiltration  to 
which  extended  reference  was  made  when  I  re- 
cently addressed  the  Los  Angeles  County  Medical 
Society,  is  responsible  for  at  least  a  part  of  the 
troubles  which  you  are  called  upon  to  treat.  Her- 
toghe  himself  mentions  the  frequency  with  which 
hypothyroidism  is  associated  with  noises  in  the 
ears  and  dizziness;  and  even  Meniere's  syndrome 
may  result  from  this  condition  of  infiltration  which 
Hertoghe  was  the  first  to  direct  to  the  attention  of 
the  profession  some  twenty  years  ago. 

I  have  encountered  several  cases  of  Eustachian 
infiltration  with  a  degree  of  deafness  which  was  at 
least  partially  due  to  this  disorder,  which  cleared 
up  when  the  quite  generalized  infiltration  was  rec- 
ognized and  its  relation  to  thyroid  inadequacy  made 
the  basis  of  the  only  proper  treatment — suitable 
thyroid  medication.  It  may  not  be  out  of  place, 
then,  if  I  should  suggest  that  any  of  the  intract- 
able aural  or  nasal  conditions  in  which  a  mucosal 
or  more  deep-seated  infiltration  might  be  present, 
should  be  a  signal  to  you  to  search  for  other  evi- 
dences of  thyroid  disorder.     In  case  any  of  them 


214  THE  INTERNAL  SECRETIONS 

are  discovered,  and  you  will  recall  that  they  are 
not  hard  to  identify,  suitable  organotherapy  profit- 
ably may  be  made  a  part  of  your  treatment.  I  am 
not  saying  that  thyroid  extract  is  a  panacea  for  in- 
tractable nose  and  throat  disorders  or  that  it  is  the 
rational  remedy  for  noises  in  the  ears  or  deafness. 
I  merely  suggest  that  if  any  of  these  symptoms 
serves  to  direct  your  attention  to  an  obscure  thy- 
roid trouble  and  you  verify  it  by  discovering  other 
symptoms  usually  expected  in  this  quite  common 
disorder,  it  is  rational  therapeutics  and  profitable 
therapeutics,  too,  to  exhibit  thyroid;  and  the  re- 
sults will  be  sufficiently  good  in  some  cases  to  make 
up  for  the  failures  in  others  and  at  the  same  time 
to  convert  one  to  the  importance  of  the  diagnostic 
and  therapeutic  value  of  this  suggestion. 

It  should  not  be  necessary  to  remind  you  that 
adenoids  are  almost  invariably  found  in  hypothy- 
roid children,  so  much  so  that  it  is  now  believed 
that  this  relation  is  not  merely  incidental,  but  that 
the  thyroid  dyscrasia  may  have  some  causative  in- 
fluence in  the  production  of  the  abnormal  growths. 
This  being  the  case,  it  seems  to  be  proper  when 
studying  adenoid  children  to  look  carefully  for 
other  evidences  of  thyroid  insufficiency  and,  when 
they  are  found,  to  treat  them  simultaneously  with 
the  adenoids.  With  the  risk  of  causing  some  slight 
offense  by  attempting  to  discuss  a  subject  with 
which  I  am  not  very  familiar,  I  will  venture  the 
statement  that  it  is  not  good  practice  to  treat  an 


IN  PRACTICAL  MEDICINE  215 

adenoid  case  by  the  mere  physical  removal  of  the 
offending  tissue,  while  the  results  of  its  presence, 
as  well  as  the  possible  causative  factors,  still  re- 
main more  or  less  definitely  present.  While  aden- 
ectomy  undoubtedly  gives  Nature  a  better  chance 
to  reassert  herself,  which  she  practically  always 
makes  the  best  use  of,  I  believe  that  suitable  or- 
gano-therapeutic  and  other  measures  will  give  her 
a  still  better  chance  if  an  insidious  thyroid  dys- 
crasia  happens  to  be  present. 

We  shall  not  have  time  to  enter  into  a  study  of 
the  broad  subject  of  the  ductless  glandular  dis- 
orders in  that  large  class  of  cases  which  McCready, 
of  Pittsburgh,  chooses  to  call  "children  requiring 
special  attention";  but  it  must  be  admitted  that  the 
first  one  to  have  an  opportunity  to  investigate  such 
cases  is  the  oto-rhinologist,  for  the  most  marked 
and  obvious  disturbance  calls  for  your  service.  Too 
often  this  service,  usually  operative,  is  all  that  is 
given  and  it  is  unfortunate.  One  should  treat  the 
whole  child  and  not  merely  that  disorder  which 
obtrudes  itself  upon  the  parent,  the  teacher  or  the 
family  physician. 

I  have  directed  your  attention  to  a  few  of  the 
conditions  in  the  nose  and  throat  which  may  be 
connected  with  hypothyroidism  and  before  I  get 
away  from  the  thyroid  gland,  there  is  another 
phase  of  its  study  that  has  recently  been  empha- 
sized. Naso-tonsillar  infections  are  a  common 
cause  of  thyroid  dyscrasias.     Those  who  have  the 


216  THE  INTERNAL  SECRETIONS 

opportunity  of  studying  many  cases  of  goiter,  both 
the  so-called  "simple"  type  and  more  especially  the 
"exophthalmic"  type,  are  beginning  to  realize  that 
overlooked  infections  of  the  mouth,  nose  or  tonsils 
are  closely  connected  with  the  incidence  of  these 
thyroid  disorders.  Some  reports  of  work  done  at 
the  University  of  Wisconsin  are  very  interesting. 
Evans,  Middleton  and  Smith  (1)  examined  the 
mouth,  nose  and  tonsils  of  three  hundred  and  sixty- 
two  individuals  with  goiter.  In  no  less  than  22  per 
cent,  of  these  there  was  a  tonsillar  endamebiasis, 
while  a  less  marked  but  indubitable  infection  of 
other  parts  of  the  mouth  and  nose  was  present  in 
a  much  larger  number.  The  importance  of  this 
was  proved  by  the  treatment  of  a  number  of  the 
cases  in  which  there  was  a  well-marked  thyroid 
dyscrasia  as  well  as  a  goiter,  and  out  of  twenty- 
three  patients  treated  with  emetine  the  dysthyroid- 
ism  was  favorably  modified  in  eighteen  cases. 

So  just  as  certain  common  symptoms  that  have 
been  mentioned  lead  us  to  think  of  thyroid  inade- 
quacy as  an  etiologic  factor  in  nose  and  throat  dis- 
orders, so  nose  and  throat  disease  may  be  a  cause 
of  well-marked  thyroid  troubles.  The  inter-relation 
is  closer  than  has  been  imagined. 

So  far  as  the  application  of  various  phases  of 
organotherapy  in  oto-rhinology  is  concerned,  we 
have  already  mentioned  some  indications  for  thy- 
roid therapy.  Certainly  it  is  worth  applying  in  some 
of  the  old,  difficult  cases  in  which  one  can  demon- 


IN  PRACTICAL  MEDICINE  217 

strate  a  more  or  less  well-marked  hypothyroidism. 
I  need  not  tell  you  of  the  value  of  adrenalin,  but 
perhaps  not  many  of  you  have  yet  had  recourse  to 
some  other  organotherapeutic  measures  for  the 
prevention  of  post-operative  hemorrhage,  especi- 
ally in  nose  and  throat  surgery.  The  first  is  the 
intramuscular  injection  of  pituitary  solution  as  a 
means  of  preventing  anticipated  bleeding.  Kahn, 
in  one  of  your  special  journals,  (2)  states  that  he 
gives  twelve  minims  of  the  standard  solution  of  the 
posterior  pituitary  principle  fifteen  minutes  before 
anesthesia  is  commenced  prior  to  nose  or  throat 
surgery.  The  above  dose  is  for  children,  fifteen 
minims  or  more  may  be  given  to  adults.  The  coag- 
ulation time  is  reduced  one-third  to  one-half  and 
hemorrhage  is  greatly  reduced,  especially  follow- 
ing turbinate  operations.  The  cardio-stimulant  in- 
fluence should  be  also  of  much  value. 

The  second  anti-hemorrhagic  remedy  is  pre- 
pared from  brain  tissue  and  has  been  named  throm- 
boplastin or  kephalin  and  is  used  locally,  being 
swabbed  on  the  cut  surface.  It  has  been  extensively 
used  by  certain  clinicians  and  further  information 
may  be  found  in  the  writings  of  Hess  (3)  and  Cro- 
nin.  (4) 

Another  interesting  and  not  very  well  studied 
phase  of  organotherapy  is  the  use  of  lymphatic 
gland  extract  in  adenoid  children.  I  am  not  setting* 
this  forward  as  something  so  valuable  that  it  should 
not  be  missed,  rather  I  am  relating  an  experience 


218  THE  INTERNAL  SECRETIONS 

which  seems  to  hold  within  it  something  of  ulti- 
mate clinical  value.  If  the  experiences  which  fol- 
low are  worked  out — and  there  are  opportunities 
galore  for  such  investigative  work — it  may  be  that 
some  new  and  illuminating  information  may  be  had 
on  the  adenoid-tonsil  question.  Ashby,  (5)  of  Liv- 
erpool, has  suggested  that  the  uniform  enlarge- 
ment of  the  tonsils  and  especially  the  growth  of 
adenoid  tissue  in  children  at  a  fairly  constant  age 
may  be  a  defensive  act  of  the  body,  the  increased 
tissue  being  an  attempt  on  the  part  of  Nature  to 
supply  some  secretion  or  substance  which  is  espe- 
cially needed  at  this  time  when  adenoid  hyper- 
trophy is  most  usual.  The  obvious  deduction  was 
that  it  might  be  possible  to  give  this  to  the  body 
just  as  the  missing  thyroid,  ovarian  or  pituitary 
substance  is  of  therapeutic  efficacy  in  conditions  of 
corresponding  glandular  insufficiency.  So  Ashby 
gave  thirty  children  one  gram  of  desiccated  lym- 
phatic gland  each  day  for  a  number  of  weeks.  There 
was  obvious  improvement,  the  hypertrophy  was  re- 
duced, snoring  ceased  and  noises  during  breathing 
disappeared.  This  is  but  a  preliminary  report  and 
is  surely  deserving  of  further  study,  for  the  oppor- 
tunities are  so  numerous  and  the  possibilities  quite 
considerable. 

Your  secretary  reminded  me  to  be  sure  to  include 
something  of  interest  to  the  ophthalmologists,  and 
before  closing,  a  word  or  two  of  posible  interest  to 
them  may  be  added.    Several  important  eye  condi- 


IN  PRACTICAL  MEDICINE  219 

tions  may  be  connected  with  ductless  glandular 
disorder.  One  of  them  is  not  yet  well  differenti- 
ated for  it  is  in  the  long  category  of  troubles  either 
due  to  or  associated  with  hypothyroidism  or,  more 
probably,  pluriglandular  insufficiency.  It  consists 
of  a  fairly  well  defined  asthenopia  of  obscure  origin 
with  a  train  of  symptoms  which  is  doubtless  famil- 
iar to  you  with  muscle  weakness  predominating. 
This  is  not  an  uncommon  condition,  and  when  the 
progressively  decreasing  powers  of  vision  are  not 
directly  connected  with  a  reasonable  cause,  and,  for 
that  matter,  even  when  a  cause  is  quite  well  de- 
fined, it  is  well  to  look  for  other  symptoms  such  as 
those  previously  mentioned  as  being  due  to  thyroid 
inadequacy.  In  such  cases  carefully  graduated  thy- 
roid mediation  may  be  of  quite  considerable  help. 

I  need  but  mention  in  passing  the  eye  findings  in 
exophthalmic  goiter,  a  typical  internal  secretory 
dyscrasia,  the  treatment  of  which  is  usually  out  of 
the  province  of  the  ophthalmologist. 

One  of  the  most  interesting  ocular  disorders  is 
the  bitemporal  hemianopsia  now  known  to  be  due 
to  pituitary  disease.  Not  uncommonly  the  oph- 
thalmologist is  the  first  to  meet  these  cases,  for  the 
sudden  or  progressive  visual  disabilities  naturally 
call  for  his  aid  first.  It  may  be  well  to  outline  in 
all  brevity  the  eye  symptoms  of  well-marked  pitu- 
itary disease.  The  enlarged  gland  in  its  sellar  cup 
causes  fairly  uniform  neighborhood  symptoms — 
we  are  not  now  interested  in  which  part  of  the 


220  THE  INTERNAL  SECRETIONS 

gland  may  be  involved,  nor  what  type  of  patholog- 
ical changes  may  be  present  and  what  varying  se- 
cretory dyscrasias  result  therefrom — and  the  chief 
among  them  affect  the  sight.  The  first  of  these  is 
due  to  the  direct  pressure  upon  the  optic  chiasm 
with  either  primary  optic  atrophy  (I  think  this 
term  is  incorrect  as  we  may  shortly  see)  or,  more 
usually,  bitemporal  hemianopsia.  This  blindness 
varies  in  degree  and  rapidity  of  onset,  but  more 
often  first  affects  the  visual  acuity  for  colors  only, 
and  later  for  form  as  well.  Professor  Cushing  very 
kindly  sent  me  last  week  a  valuable  monograph  by 
himself  and  C.  B.  Walker,  (6)  in  which  the  distor- 
tions of  the  visual  field  from  brain  tumors  are  in- 
terestingly considered.  The  conclusion  of  this 
study  is  worth  reiterating:  Detailed  perimetry  with 
small  test  objects  of  several  sizes  is  advocated  for 
patients  with  pituitary  disease  in  order  that  stages 
of  hemianopsia  antecedent  to  those  usually  recog- 
nized may  be  detected. 

The  other  eye  symptoms  are  found  in  more 
marked  cases,  i.  e.,  when  the  pituitary  tumor  ex- 
tends beyond  the  sellar  edges.  In  such  cases  there 
may  be  paralysis  of  both  of  the  external  recti  with 
resulting  internal  strabismus  due  to  pressure  on  the 
sixth  cranial  nerve,  or  by  similar  pressure  on  the 
third  cranial  nerve  external  strabismus  may  result. 
Still  later  the  increased  intracranial  pressure  will 
cause  choked  disc  and  ultimate  total  blindness. 
This  condition  and  the  so-called    "primary    optic 


IN  PRACTICAL  MEDICINE  221 

atrophy''  (of  pituitary  origin)  or  descending  at- 
rophy does  not  necessarily  mean  an  anatomical  de- 
generation of  the  nerves,  but  according  to  Cushing 
(loc.  cit.)  it  is  very  often  only  a  "physiological 
block  to  the  transmission  of  the  visual  impulses" 
which  may  be  relieved  speedily  by  decompression 
or  other  more  serious  surgical  measures. 

As  in  all  other  phases  of  medical  endeavor  the 
ramifications  of  the  internal  secretory  threads  are 
closely  intertwined  with  every  phase  of  physiolog- 
ical activity  and  as  the  skein  is  unravelled  and  our 
understanding  of  these  interrelations  becomes  more 
comprehensive,  there  comes  a  better  control  of 
many  conditions,  the  treatment  of  which  has  been 
beset  previously  with  seemingly  insurmountable 
difficulties.  Enthusiasm  in  the  study  of  the  inter- 
nal secretory  organs  and  their  disorders  is  not  to 
be  scorned,  for  it  leads  one  into  fields  in  which 
many  of  the  flowers  "born  to  blush  unseen  and 
waste  their  sweetness  on  the  desert  air"  may  be 
viewed,  handled  and  appreciated  as  never  before. 

REFERENCES 

1.  Evans,  Middleton  and  Smith:     Amer.  Jour.  Med. 
Sciences,  February,  1916  cli,  p.  210. 

2.  Kahn :     Ann.    Otol.,  Rhinol.  and    Laryngol.,  June, 
1915. 

3.  Hess:     Jour.   Amer.    Med.   Assn.,   April   24,    1915, 
p.  1395. 

4.  Cronin :     Ibid.,  February  19,  1916,  p.  557. 

5.  Ashby:    British  Med.  Jour.,  1913,  i,  p.  1159. 

6.  Cushing  and  Walker:     Brain,  March,  1915,  xxxvii, 
p.  341. 


XVIII 

THE  TREATMENT  OF  RICKETS 

RICKETS  is  a  nutritional  disorder  of  children,  a 
form  of  starvation,  hence  before  it  can  be  treated 
effectively  we  must  know  what  factors  are  promi- 
nent in  the  production  of  the  disturbed  metabolism 
and  what  elements  can  be  given  acceptably  to  re- 
place those  that  are  deficient.  From  an  experi- 
mental standpoint,  rickets  is  now  understood  to  be 
a  result  of  endocrine  disorder.  It  has  been  pro- 
duced more  easily  and  quickly  by  the  removal  or 
destruction  of  certain  of  the  glands  of  internal  se- 
cretion than  by  dietetic  restriction.  In  fact,  the 
dietetic  element  in  the  etiology  of  rickets  seems  to 
be  losing  a  good  share  of  the  importance  that  was 
until  recently  attributed  to  it. 

Direct  medication.  Five  things  need  to  be  ac- 
complished: 

1.  Replace  the  missing  mineral  element  in  the 
blood  and  bones — calcium.  The  best  calcium  salt 
is  the  phospate,  which  is  conveniently  given  in  the 
U.  S.  P.  syrup  of  calcium  lactophosphate,  two 
drams,  three  to  six  times  a  day. 

2.  Replace  the  missing  vitamines,  factors  which 
are  now  being  recognized  as  playing  an  important 
part  in  many  nutritional  disorders.  In  nursing  chil- 


Prize  Question  No.  CLXVII,  for  which  a  prize  of  $25.00 
was  received  from  the  editors  of  the  New  York  Medical  Journal. 
Published  in  the  N.  Y.  Med.  Jour.  April  1,  1916.  (Copyright 
1916  by  A.  R.  Elliott  Publishing  Company.) 

(222) 


IN  PRACTICAL  MEDICINE  223 

dren  with  serious  malnutrition  it  is  often  noted  that 
the  mother  is  badly  nourished,  and  suitable  treat- 
ment will  augment  the  value  of  her  milk.  In  thera- 
peutics this  is  accomplished  by  suitable  dietetic  reg- 
ulation and  by  organotherapy. 

3.  Antagonize  a  tendency  to  acidosis  which  is 
invariably  present  in  rhachitic  children  and  is  quite 
frequently  overlooked.  Sodium  citrate  is  excellent 
for  this  purpose  and,  incidentally,  when  given  with 
milk,  it  prevents  the  formation  of  large  curds  and 
thus  favors  digestion.  When  the  urinary  acidity  is 
high,  sodium  bicarbonate  may  be  given  in  small  and 
frequent  doses,  well  diluted  and  so  timed  as  not  to 
interfere  with  digestion;  though  the  citrate  has  an 
almost  equal  neutralizing  value. 

4.  Enhance  the  mineral  content  of  the  blood.  In 
addition  to  the  calcium  salts  we  can  advantage- 
ously give  the  salts  secured  from  fresh  vegetables. 
This  is  an  extremely  important  part  of  the  suc- 
cessful treatment  of  rickets,  for  these  saline  ele- 
ments seem  to  be  urgently  needed  by  the  system; 
and  are  easily  prepared  and  assimilated.  In  France 
bone  substance  is  used  not  uncommonly  and  per- 
haps there  is  some  advantage  in  this  organic  form 
of  calcium.  Until  recently  preparations  of  bone 
(not  bone  marrow)  were  difficult  to  secure  but  Rus- 
sell of  New  York  has  lately  produced  a  prepara- 
tion of  green  bone  which  should  be  as  much  better 
than  the  powdered  bone  as  it  is  better  than  the 
ordinary  mineral  salts  we  usually  prescribe. 


224  THE  INTERNAL  SECRETIONS 

5.  Favor  the  restoration  of  the  conditions  which 
cause  or  aggravate  the  disturbed  mineral  metabo- 
lism. This  is  best  accomplished  by  suitable  organo- 
therapy. Many  times  small  doses  of  thyroid  ex- 
tract— one  quarter  to  one  half  grain,  three  times  a 
day — will  influence  the  nutrition  of  the  rhachitic 
child  in  a  most  decided  manner.  Thymus  extract 
has  been  recommended  upon  the  theoretical  ground 
that  the  thymus  controls  calcium  metabolism  and 
that  rickets  is  possibly  a  manifestation  of  hypo- 
thymism,  for  a  characteristic  result  of  thymectomy 
in  young  animals  is  a  typical  rickets  with  marked 
softening  and  bending  of  the  long  bones,  especially 
of  the  legs;  and  many  autopsies  of  children  dying 
with  rickets  show  the  thymus  to  be  atrophied  pre- 
maturely. Again,  pituitary  is  occasionally  recom- 
mended, while  total  adrenal  substance  has  facili- 
tated recovery  after  other  measures  had  been  tried 
with  little  or  no  benefit. 

The  stimulation  of  the  endocrine  glands  is  a 
matter  of  special  importance,  as  unless  this  is  done 
the  calcium  salts  given  simultaneously  may  be  ex- 
creted and  thus  be  useless,  for  it  is  certain  that  the 
fundamental  factor  in  rickets  is  not  so  much  a  de- 
ficiency of  calcium  as  an  inability  to  fix  and  utilize 
it.  This  capacity  is  undoubtedly  under  the  control 
of  the  ductless  glands,  those  just  mentioned  being 
the  most  important. 

Pluriglandular  therapy  is  a  useful  even  if  empiric 
procedure  in  rickets.    The  following  combination  is 


IN  PRACTICAL  MEDICINE  225 

well  worth  trying: 

Total  adrenal  substance 2  parts ; 

Desiccated  thyroids  1  part ; 

Thymus  gland  3  parts ; 

Excipient  to  make 10  parts. 

Two  or  more  grains  of  this  mixture,  depending 
upon  the  age  of  the  child,  may  be  given  three  times 
a  day.  The  proportions  may  be  varied,  or  pituitary 
substance  (total)  may  replace  one  part  of  the  ex- 
cipient. A  total  of  one  and  a  half  to  two  grains 
each  of  thyroid  and  adrenal,  and  ten  grains  of 
thymus  may  be  given  in  twenty-four  hours.  Car- 
pani  (Lancet,  June  19,  1915)  recommends  pluri- 
glandular therapy  in  rickets  and  gives  powdered 
and  dried  gland  substances  in  toto,  in  doses  suitable 
to  the  age,  in  milk,  for  fifty  days,  omitting  this  for 
one  week  after  the  first  month's  treatment.  He 
noticed  rapid  and  striking  improvement,  especially 
early  in  the  treatment,  the  benefit  first  noticed  in 
the  digestion,  then  in  the  nervous  manifestations, 
and  later  in  the  blood  and  osseous  system. 

Another  form  of  organotherapy  which  is  quite 
generally  used,  is  the  administration  of  codliver  oil 
alone  or  in  various  forms  and  combinations.  The 
benefit  is  not  due  merely  to  the  easily  assimilated 
hydrocarbons,  but  also  to  the  vitamines  which  are 
present  and  to  a  substance  of  a  hormone  nature 
which  apparently  aids  in  the  metabolism  of  lime 
salts.  Parenthetically  it  may  be  remarked  that 
these  substances  are  present  in  greater  quantities  in 
the  cruder  products,  thus  explaining  the  statements 


226  THE  INTERNAL  SECRETIONS 

of  Leonard  Williams  and  others  to  the  effect  that 
the  cruder  the  oil,  the  better  its  therapeutic  effects 
in  many  cases. 

Hygienic  care.  Obviously  the  general  care  of 
rhachitic  children  should  be  as  good  as  possible. 
Good  hygiene  favors  all  treatment,  and  usually  chil- 
dren suffering  with  rickets  have  not  had  the  home 
care  they  needed.  The  emunctories  must  be  watched 
and  regulated  by  the  diet,  by  an  occasional  dose  of 
castor  oil,  and,  at  the  beginning  of  the  treatment,  by 
calomel  in  divided  doses.  The  skin  and  circulation 
should  be  stimulated  by  daily  cool  bathing  with 
friction.  Sodium  bicarbonate  in  the  water  (a  heap- 
ing teaspoonful  to  each  quart)  is  often  an  advan- 
tage, especially  where  the  skin  is  chafed.  Gentle 
massage  with  almond  or  olive  oil  is  valuable.  Sun- 
shine, fresh  air,  suitable  exercise,  and  regular  rest 
are  all  important,  especially  the  first  two. 

Dietetic  management.  Most  rhachitic  children 
have  been  poorly  fed  and  the  malnutrition  is  not 
confined  to  the  bones.  Digestion  is  poor  and  assim- 
ilation is  reduced.  Fresh  milk,  because  of  its  rich- 
ness in  vitamines  and  "living  salts,"  is  by  far  the 
best  food.  Pasteurized  milk  is  a  poor  substitute, 
prepared  foods  are  usually  unsatisfactory,  and 
boiled  milk  is  the  worst  food  that  could  be  selected. 
The  value  of  sodium  citrate  has  already  been  men- 
tioned, and  lime  water  is  also  useful  in  modifying 
the  milk.  Limits  of  space  forbid  a  discussion  of 
the  necessary  milk  modification  and  its  administra- 


IN  PRACTICAL  MEDICINE  227 

tion.  Suffice  it  to  say  that  the  child  must  be  fed 
with  milk  modified  on  the  basis  of  its  weight,  not 
its  age — at  least  until  digestion  is  normal  and  the 
child  is  obviously  improving.  At  this  stage  barley 
gruel,  oatmeal  gruel,  corn  flakes,  and  other  "heav- 
ier" cereal  foods  may  be  added,  and  later  potatoes 
(baked)  and  other  foods  as  a  tolerance  for  them  is 
established. 

Between  meals  plenty  of  fluid  should  be  given, 
and  it  should  be  planned  to  carry  in  this  as  many  of 
the  assimilable,  vegetable  mineral  salts  as  conve- 
niently can  be  given.  Small  quantities  of  fruit 
juices,  especially  orange  and  prune,  may  be  given 
two  or  more  times  a  day.  Often  idiosyncrasies  to 
these  are  found,  hence  the  need  for  caution. 

Another  excellent  dietetic  adjuvant,  I  might  bet- 
ter say  therapeutic  measure,  is  clear  vegetable  soup. 
Sometimes  it  may  accomplish  more  than  any  of  the 
direct  remedies  mentioned  previously,  since  it  con- 
tains Nature's  minerals,  which  normally  form  the 
inorganic  pabulum  of  the  cells.  The  preparation  of 
this  soup  is  important,  and,  incidentally,  it  will  be 
found  a  most  valuable  remedy  in  many  metabolic 
dyscrasias  in  adults  as  well  as  children,  including 
rheumatism,  malnutrition,  certain  neurasthenic 
conditions,  etc. 

Spinach,  potatoes  (or  well  cleaned  potato  par- 
ings), carrots,  turnips,  fresh  peas  (with  the  pods), 
and,  perhaps,  small  amounts  of  onions,  are  washed, 
cut  up,  and  covered  with  two  or  three  times  their 


228  THE  INTERNAL  SECRETIONS 

volume  of  water.  Raw  wheat  or  bran  may  take  the 
place  of  one  or  more  of  these  vegetables,  if  desired. 
The  exact  ingredients  or  their  relative  amounts  are 
not  of  such  great  moment.  Simmer  for  three  or 
more  hours  over  a  slow  fire,  or,  better  still,  boil 
briskly  for  fifteen  minutes  and  place  in  a  fireless 
cooker  for  three  to  five  hours.  Strain  without  pres- 
sure. The  remainder  may  be  passed  through  a  sieve 
and  used  as  a  basis  for  a  palatable  thick  soup  for 
the  table.  One  to  four  ounces  of  this  clear  liquid 
may  be  given  four  times  a  day,  with  or  between  the 
feedings.  Bran  water  may  be  used.  It  is  pre- 
pared and  given  in  approximately  the  same  way. 

The  surgical  care  of  deformed  bones  is  a  matter 
for  the  attention  and  care  of  the  orthopedist. 
Braces  may  be  helpful,  osteoclasis  is  often  advis- 
able; but  in  any  event  the  foregoing  suggested  out- 
lines for  the  treatment  must  be  associated  with  sur- 
gical care. 


XIX 

THE  ORAL  ADMINISTRATION  OF 
ADRENALIN 

THE  active  chemical  entity  prepared  from  the 
adrenal  medulla  is  oxidized  and  destroyed  very 
easily  in  the  body.  This  accounts  for  the  ephemeral 
effects  which  follow  its  administration  as  a  remedy; 
and  also  the  comparative  rarity  of  the  symptom 
complex  of  hyperadrenia.  In  vitro  adrenalin  is 
quickly  destroyed  by  numerous  reagents  and  it  has 
also  been  shown  that  it  loses  its  activity  when  in 
contact  for  a  short  time  with  the  gastric  juice.  If 
adrenalin  is  given  by  mouth,  and  the  stomach  is 
evacuated  ten  minutes  later,  it  is  usually  impos- 
sible to  detect  this  substance.  In  the  fasting  stom- 
ach this  disintegration  is  accomplished  in  almost 
the  same  time,  though  here  the  writer  is  by  no 
means  sure  that  this  really  means  that  the  adren- 
alin is  destroyed,  for  some  of  it  is  absorbed. 

All  these  experiences  have  led  to  a  quite  natural 
impression  that  adrenalin  was  not  effective  when 
given  by  mouth,  and  that  to  obtain  other  than  the 
well  known  results,  it  must  be  given  by  hypodermic 
or  intravenous  injection.  There  are  not  a  few  ref- 
erences in  medical  literature,  including  that  of  the 
manufacturers,  which  indicate  that  this  idea  is  well 
grounded  in  the  minds  of  the  profession. 


Reprinted  from  the  New  York  Medical  Journal,  November 
4,  1916.  (Copyright,  1916,  by  A.  R.  Elliott  Publishing  Com- 
pany.) 

(229) 


230  THE  INTERNAL  SECRETIONS 

For  years  I  have  been  convinced  by  personal  ex- 
periences that  this  opinion  was  misleading,  and  am 
confident  that  unquestioned  therapeutic  effects 
have  followed  the  oral  administration  of  adrenalin. 

In  a  short  communication  to  the  editors  of  the 
New  York  Medical  Journal  (July  8,  1916,  p.  94) 
Leland  Boogher  relates  some  interesting  personal 
experiences  following  the  use  of  fifteen  minims  of 
adrenalin  solution  (presumably  the  standard  one  in 
1,000  solution)  in  a  tablespoonful  of  water  by 
mouth  for  the  relief  of  excruciating  abdominal  pain 
due  to  an  abscess  in  the  transverse  colon.  Boogher 
has  since  recommended  this  measure  as  an  anal- 
gesic remedy  for  gallstone  and  renal  colic,  and  "it 
gave  splendid  relief."  This  reference  emphasizes 
what  is  probably  an  original  application  of  this 
much  used  remedy;  and  credit  for  this  should  be 
given  to  Dr.  George  Richter,  of  St.  Louis,  who  pre- 
scribed the  treatment  outlined  above. 

However,  this  experience  is  also  corroborative 
evidence  of  a  well  established  fact,  still  denied  in 
many  quarters,  that  adrenalin  per  os  is  both  potent 
and  useful.  In  American  Medicine  a  number  of 
items  have  been  reported  which  substantiate  this 
view.  In  the  issue  for  April,  1915  (p.  253),  there 
appears  an  article  entitled  "Giving  Organothera- 
peutic  Products  by  Mouth,"  by  the  writer,  in  which 
reference  is  made  to  the  prevalent  but  mistaken  no- 
tion as  to  the  availability  of  many  organothera- 
peutic  extracts  when  given  per  os.     Reference  was 


IN  PRACTICAL  MEDICINE  231 

there  made  to  a  statement  to  the  effect  that  "these 
(organotherapeutic)  extracts,  with  the  possible  ex- 
ception of  thyroid,  are  destroyed  in  the  stomach; 
hence  it  is  useless  to  give  them  unless  hypodermic- 
ally."  The  writer  then  proceeded  in  the  following 
terms:  "This  is  not  true,  and  the  statement  can 
be  easily  disproved.  .  .  .  Why,  if  organothera- 
peutic remedies  generally  are  destroyed  by  the  di- 
gestive juices,  should  thyroid  be  the  lone  exception 
to  the  rule?  Wherein  does  the  active  principle  of 
the  thyroid  differ  in  its  absorbability  or  destructi- 
bility  from  the  hormones  of  the  adrenals,  pituitary, 
or  gonads?  The  most  conclusive  and  practical 
proof  of  the  inaccuracy  of  such  a  position  would 
be  to  have  those  who  make  such  statements  (or  be- 
lieve them)  take,  say,  an  ounce  of  one  in  1,000  ad- 
renalin chloride  solution — it  contains  less  than  half 
a  grain  of  the  active  principle — and  note  carefully 
if  there  is  not  a  considerable  modification  of  the  cir- 
culatory equilibrium!" 

Several  of  the  statements  as  to  the  destructibility 
of  adrenalin  when  given  by  mouth  appear  in  the 
scientific  publications  of  the  American  Medical  As- 
sociation, though,  curiously  enough,  in  the  weekly 
department  on  Therapeutics  in  the  Journal  A.  M. 
A.  (October  16,  1915,  p.  1366)  there  is  a  brief  con- 
sideration of  the  emergency  treatment  of  sudden 
cardiac  failure  from  which  the  following  statement 
is  cited:  "Epinephrine  may  be  given  in  a  dose  of 
five  drops  on  the  tongue,  which  may  be  repeated  in 


232  THE  INTERNAL  SECRETIONS 

half  an  hour  if  advisable.  .  .  .  All  of  the  fore- 
going (including  strychnine,  hot  coffee,  camphor, 
etc.)  are  quick  acting  treatments."  This  casual 
statement  is  of  unusual  interest,  since  the  use  of 
epinephrine  (which,  by  the  way,  is  not  obtainable 
on  prescription,  as  there  is  no  such  preparation  on 
the  market,  but  is  presumably  intended  to  mean 
adrenalin)  is  advised  to  be  given  by  the  mouth, 
contradicting  statements  in  the  Journal  A.  M.  A. 
and  elsewhere  which  indicate  that  this  drug  is  use- 
less given  in  this  manner;  and  here,  be  it  noted, 
this  remedy,  in  a  dose  of  only  five  drops  on  the 
tongue,  is  classed  as  a  "quick  acting"  cardiac  stim- 
ulant. 

There  are  a  number  of  other  references  to  the 
effective  administration  of  adrenalin  by  mouth,  a 
few  of  which  will  be  referred  to  shortly.  It  should 
be  understood,  however,  that  such  fundamental  er- 
rors as  the  one  under  discussion  are  due  to  the 
drawing  of  conclusions  from  laboratory  experi- 
ments alone.  We  grant  that  adrenalin  is  "digested" 
in  the  test  tube.  It  is  easy  to  prove  that  it  cannot 
be  recovered  from  the  gastric  contents  after  being 
in  the  stomach  for  only  a  short  time.  None  will 
deny  that  it  is  rapidly  and  thoroughly  oxidized.  But 
adrenalin  is  also  very  easily  absorbed,  as  every 
rhinologist  knows  and  as  any  physician  can  quickly 
find  out  if  he  cares  to  hold  a  dram  or  two  in  his 
mouth  for  a  few  minutes.  Is  it  not  possible,  then, 
as  the  writer  suggests,  that  the  factor  of  destruc- 


IN  PRACTICAL  MEDICINE  233 

tion  in  the  stomach  is  not  concerned  at  all,  but  that 
much  or  all  of  the  active  principle  is  taken  up  by 
the  mucous  membrane  of  the  mouth,  palate,  esoph- 
agus, and  cardia,  thus  enabling  it  to  exert  its  thera- 
peutic effects  and  to  maintain  its  reputation  as  a 
"quick  acting"  remedy  when  given  by  mouth? 

In  connection  herewith  it  should  be  recalled  that 
the  administration  of  hormones — and  adrenalin  is 
certainly  a  hormone  and  has  been  quite  properly 
called  the  "chromaffin  hormone" — brings  about 
physiological  effects  in  two  ways:  First,  by  the  di- 
rect action  of  that  part  of  the  actual  substance  ad- 
ministered; and,  second,  by  the  increased  produc- 
tion by  the  organism  of  the  hormone  correspond- 
ing to  that  which  is  given.  In  other  words,  when 
we  give  adrenalin,  not  only  do  we  get  the  direct 
drug  effect  from  the  dose  which  is  absorbed,  but  at 
the  same  time  we  are  increasing  the  capacity  of  the 
adrenal  medulla  to  produce  more  of  its  chromaffin 
hormone. 

We  know,  from  many  experiences  with  thyroid 
therapy,  that  with  a  presumably  normal  or  even  a 
slightly  deficient  thyroid,  certain  doses  of  thyroid 
extract  will  bring  about  symptoms  of  hyperthy- 
roidism the  results  of  which  are  not  directly  due  to 
the  drug  administered,  but  to  the  increased  thyroid 
activity,  and  these  results  remain  long  after  the 
comparatively  small  amounts  of  thyroid  which 
were  given  have  been  used  up.  This  shows  that  the 
principle  of  homostimulation  applies  to  normal  as 


234  THE  INTERNAL  SECRETIONS 

well  as  disordered  glands,  and  this  is  just  as  pos- 
sible with  the  adrenals  as  with  the  thyroid. 

To  lend  emphasis  to  the  position  taken  by  the 
writer,  as  well  as  to  Boogher's  brief  but  interesting 
communication,  a  few  clinical  reports  from  recent 
literature  may  be  collated  here  with  advantage: 

Hutinel  (Arch,  de  med.  des  enfants,  February 
and  March,  1915)  recommends  three  or  four  drops 
of  adrenalin  solution  one  in  1,000,  diluted,  every 
two  or  three  hours,  as  a  part  of  the  treatment  of 
severe  infectious  diseases  in  children.  Each  child 
may  receive  as  much  as  twenty  minims  a  day  by 
mouth,  and  Hutinel  remarks  that  he  has  never  ob- 
tained so  much  benefit  from  the  usual  supporting 
measures  and  that  the  effects  are  remarkable  even 
in  the  gravest  cases,  since  the  blood  pressure  is  in- 
creased and  there  is  an  immediate  response  in  the 
general  mental  and  physical  condition,  while  the 
pulse  rate  is  reduced  and  diuresis  is  favored. 

M.  H.  Smith  (Medical  Record,  October  2,  1915, 
p.  586)  reports  having  successfully  treated  several 
cases  of  Rocky  Mountain  spotted  fever  with  ten 
drop  doses  of  adrenalin  solution  every  four  hours. 
This  obviated  the  prostration  common  in  these 
cases,  convalescence  was  established  earlier  than 
usual,  and  there  was  an  apparent  beneficial  effect 
upon  the  course  of  the  disease.  That  the  remedy 
given  by  mouth  was  "quick  acting"  is  emphasized 
by  Smith's  remark  that  within  a  few  minutes  of 
the  administration  of  each  dose,  a  fullness  of  the 


IN  PRACTICAL  MEDICINE  235 

pulse  and  a  fading  of  the  eruption  were  noticeable. 

Not  much  has  been  done  in  this  country  with  the 
use  of  adrenalin  for  the  treatment  of  nephritis, 
though  at  least  five  articles  have  appeared  in  cur- 
rent Italian  medical  literature  speaking  well  of  this 
method.  The  most  recent  reference  is  abstracted 
in  the  Journal  A.  M.  A.,  June  10,  1916.  This  ab- 
stract from  II  Policlinico  (April  30,  1916)  may  be 
cited  in  full:  "Borelli  reports  two  cases  of  acute 
and  one  of  chronic  nephritis  in  which  remarkable 
benefit  was  realized  by  epinephrine*  treatment. 
One  patient  was  a  child  of  nearly  five  years,  the 
others  were  men  of  fifty  and  sixty-two.  He  gave 
the  child  sixteen  drops  a  day  of  a  one  in  1,000  solu- 
tion of  epinephrine,  four  drops  at  four  hour  inter- 
vale. The  adults  were  given  forty  drops  a  day, 
eight  at  a  time.  Ercolani  called  attention,  in  1910, 
to  the  benefit  from  epinephrine  by  the  mouth  in 
nephritis,  commending  the  harmlessness,  ease,  and 
efficacy  of  this  method  of  treating  kidney  disease, 
which  has  proved  its  usefulness  again  and  again, 
and  Borelli's  experience  has  confirmed  this." 

Previous  to  this  report  another  exhaustive  study 
on  the  subject  was  published  by  Silvestri  (Gaz.  d. 
osp.  e  d.  clin., ^September  1,  1915),  in  which  he  ana- 
lyzes the  reports  of  a  number  of  other  clinicians, 
adds  several  personal  experiences,  and  proves  that 


♦"Epinephrine"  is  the  term  used  uniformly  in  all  the  pub- 
lications of  the  American  Medical  Association,  although  in  this 
instance  the  title  of  Borelli's  original  article  is:  "Cura  della 
nefrite  con  la  soluzione  di  adrenalina  nella  pratica  di  condotta." 


236  THE  INTERNAL  SECRETIONS 

adrenalin  is  a  most  valuable  aid  in  the  acute  stages 
of  nephritis,  but  of  little  value  in  chronic  condi- 
tions. He  also  tells  of  the  experiences  of  Fede,  who 
found  this  procedure  comparatively  more  effective 
in  children,  since  in  them  the  elasticity  of  the  renal 
glomeruli  and  tubules  is  greater,  while  the  adrenal 
glands  are  proportionally  larger  in  children  than  in 
adults  (presumably  being  more  susceptible — quan- 
titatively— to  the  homostimulant  action  referred  to 
previously).  Silvestri  suggests  that  1  or  2  minims 
of  the  1 :1000  solution  of  adrenalin  chloride  be 
dropped  on  the  tongue  every  three  hours — the  total 
amount  given  being  regulated  by  the  clinical  re- 
sponse.   For  adults  the  dose  may  be  larger. 

There  are  also  numerous  reports  in  the  literature 
of  the  therapeutic  efficacy  of  total  adrenal  gland, 
and  of  course  this  is  given  per  os  in  tablet  form.  In 
a  recent  monograph  on  "Drug  Therapy  of  Cardio- 
vascular Diseases,"  Satterthwaite  (Int.  Clinics,  1, 
1916,  p.  26)  recommends  desiccated  adrenal  gland 
as  a  useful  vasomotor  tonic  in  doses  of  two  and  a 
half  grains  three  times  a  day,  and  remarks  that 
single  doses  as  a  rule  will  relieve  palpitation  in  a 
comparatively  short  time.  The  active  principle  of 
the  desiccated  gland  is  naturally  similar  to  that 
which  is  available  in  a  pure  state,  and  the  favorable 
experiences  with  total  adrenal  gland  therapy,  by 
mouth  of  course,  is  additional  proof  that  the  posi- 
tion of  those  who  have  contended  that  the  oral  ad- 
ministration of  adrenalin  is  useless,  is  fallacious. 


XX 

THE  ADJUNCT  TREATMENT  OF 
TUBERCULOSIS  WITH  CERTAIN  ORGANIC 

EXTRACTS 

AS  the  years  go  by  our  ideas  regarding  the  treat- 
ment of  tuberculosis  are  modified,  and  in  no  phase 
of  therapeutics  do  opinions  change  so  much.  About 
1890  Professor  Koch  discovered  a  therapeutic  won- 
der in  tuberculin,  but  its  vogue  was  short-lived,  for 
the  intricacies  of  dosage  had  not  then  been  learned. 
Less  than  ten  years  ago  hyperalimentation  was  the 
fashion,  and,  as  with  fashions  in  other  things,  it 
was  carried  to  extremes.  Nowadays  tuberculin  has 
regained  its  place,  but  its  application  is  almost  an 
obsession,  and  the  devotion  of  some  practitioners 
to  tuberculin  in  one  form  or  another  seems  to  show 
that  the  fashion  has  changed  again. 

There  appears  to  be  an  idea,  almost  universal, 
that  as  tuberculosis  is  an  invasion  of  the  body  by  a 
certain  bacillus,  the  treatment  must  needs  be  di- 
rected primarily  towards  the  destruction  of  these 
organisms  and  the  neutralization  of  their  toxic 
products.  That  this  is  essential  none  will  deny, 
but,  unfortunately,  the  view  is  much  too  narrow. 
Tuberculosis  is  first  and  foremost  a  condition  of 
lowered  resistance  in  which  the  infective  process 
has  become  so  prominent  as  quite  to  overshadow 


British  Journal   of  Tuberculosis    (London),    1913,   Vol.   vii. 
p.  170. 

(237) 


238  THE  INTERNAL  SECRETIONS 

the  original  and  by  far  the  most  important  defect. 
The  following  extract  from  a  recent  editorial  (1) 
aptly  states  the  matter  in  the  plainest  of  language: 

"The  cause  of  active  tuberculosis  must  now  be 
sought  in  something  which  destroys  our  tolerance, 
and  permits  our  own  lesions  to  develop.  Chief 
among  these  causes  are  the  acute  infections.  .  .  . 
In  addition  to  these  infections  anything  else  which 
lowers  the  general  health  may  thus  interfere  with 
that  constant  production  of  antibodies  upon  which 
our  tolerance  depends.  We  can  definitely  trace 
many  cases  to  a  long  period  of  overwork,  alcoholic 
excesses,  exposure  to  wet,  or  adverse  climate  con- 
ditions. Indeed,  anything  which  interferes  with  a 
perfect  condition  of  health  may  allow  the  spread 
of  a  focus  of  infection  which  we  had  carried  around 
for  a  half  century  or  more.  Even  senility  itself  may 
do  this.  Many  men  carry  the  pneumococcus  in  their 
mouths  all  their  lives,  only  to  be  killed  by  it  in  the 
end;  and  we  must  now  look  upon  the  tubercle  bacil- 
lus in  the  same  light  of  a  constant  companion, 
harmless  as  long  as  we  remain  in  good  condition, 
but  a  malignant  enemy  the  instant  our  guards  are 
lowered." 

It  is  admitted  that  the  good  results  of  the  hygi- 
enic methods  at  present  in  vogue  are  evidence  that 
a  general  building  up  and  restoring  of  the  vitality 
is  needed,  but,  after  all,  is  not  this  merely  a  passive 
form  of  resistance?  Some  more  active  adjunct 
would  be  welcome,  and  it  is  believed  that  such  will 


IN  PRACTICAL  MEDICINE  239 

be  found  in  a  consideration  of  the  internal  secre- 
tions as  well  as  of  the  possibilities  of  organotherapy 
as  an  auxiliary  method  of  treatment. 

Arnold  Lorand,  in  his  interesting  book  "Old  Age 
Deferred/'  points  out  that  when  the  usual  sanato- 
rium treatment  is  having  its  good  effects  there  is  a 
local  disintoxication,  and  the  cells  of  the  lungs  are 
co-operating  in  this  process  in  a  manner  analogous 
to  the  internal  secretion  by  the  cells  of  other  gland- 
ular structures.  This  may  be  one  reason  for  the 
fleeting  advocacy  by  some  of  extract  of  lung-tissue 
as  a  remedy  in  pulmonary  disorders.  (2,  3)  Lorand 
continues: 

"It  is  a  positive  fact  that  under-nutrition  (or  de- 
fective nutrition)  through  lack  of  the  necessary 
amount  of  proteids  in  the  diet  exposes  one  more  to 
infection  by  the  bacilli.  .  .  .  The  findings  of  Gra- 
witz  indicate  that  an  insufficient  proteid  diet  pre- 
disposes also  to  anemia.  The  importance  of  this 
fact  is  emphasized  by  Sajous,  who  has  shown 
(1903)  that  defective  nutrition  weakens  the  activ- 
ity of  the  pituitary,  thryoid  and  adrenals,  the  secre- 
tions of  which  take  an  active  part  in  the  destruction 
of  bacteria  and  their  toxins."  (4) 

The  usual  general  manifestations  almost  invari- 
ably present  in  cases  of  tuberculosis — fever,  lassi- 
tude, and  diminished  metabolism — can  not  but  be 
accompanied  by  disturbances  of  a  similar  nature 
in  the  work  of  the  internal  secretory  organs.  Per- 
haps the  importance  of  these  functions,  many  of 


240  THE  INTERNAL  SECRETIONS 

which  are  as  yet  little  understood,  is  even  greater 
than  we  think,  and  certain  facts  can  bear  much 
emphasis  and  repetition.  Professor  Schafer,  in  his 
presidential  address  before  the  British  Association, 
June,  1912,  (5)  says:  "The  second  essential  condi- 
tion for  the  maintenance  of  the  life  of  the  cell- 
aggregate  is  the  co-ordination  of  its  parts  and  the 
due  regulation  of  their  activity,  so  that  they  may 
work  together  for  the  benefit  of  the  whole.  .  .  . 
The  activities  of  the  cells  constituting  our  bodies 
are  controlled  in  another  way  than  through  the 
nervous  system — viz.,  by  chemical  agents  circulat- 
ing in  the  blood.  .  .  .  These  substances  have  re- 
ceived the  general  designation  of  'hormones,'  a 
term  introduced  by  Professor  Starling.  Their 
action,  and  indeed  their  very  existence,  has  only 
been  recognized  of  late  years,  although  the  part 
which  they  play  in  the  physiology  of  animals  ap- 
pears to  be  only  second  in  importance  to  that  of  the 
nervous  system  itself;  indeed,  maintenance  of  life 
may  become  impossible  in  the  absence  of  certain  of 
these  hormones." 

When  we  consider  all  the  emphasis  that  has  been 
laid  upon  the  importance  of  the  internal  secretions, 
it  seems  strange  that  their  relation  to  tuberculosis 
is  rarely  mentioned.  Treatment  based  upon  the 
regeneration  or  regulation  of  these  important 
glandular  functions  is  quite  the  exception,  and  will 
continue  to  be  until  the  importance  of  their  rela- 
tion to  the  original  cause  of  tuberculosis  is  realized. 


IN  PRACTICAL  MEDICINE  241 

Our  French  colleagues,  always  more  alert  in  the 
application  of  measures  "on  the  border-line  of 
progress  in  therapeutics,"  have  for  some  years  been 
emphasizing  the  importance  of  "Les  Opotherapies 
dans  la  Tuberculose,"  and  a  valuable  resume  with 
the  above  title  was  recently  published.  (6)  In  this 
article  reference  is  made  to  no  less  than  fourteen 
distinct  forms  of  opotherapy,  of  which  perhaps 
only  one — the  use  of  red  bone-marrow — has  found 
any  favor  in  England  and  America. 

It  would  seem  that  the  most  important  phase  of 
the  organotherapy  of  tuberculosis  is  unquestion- 
ably the  use  of  spleno-pancreatic  extracts.  Next  in 
importance  is  the  use  of  preparations  from  the  liver, 
and  the  value  of  these  methods  is  enhanced  by  the 
administration  of  secretin — a  hormone  prepared 
from  the  pylorus  and  duodenum. 

With  the  use  of  extracts  of  thyroid,  pituitary,  ad- 
renal, lung,  ovary,  and  testes,  I  have  had  no  experi- 
ence, and  although  numerous  references  to  these 
various  subjects  can  be  found  in  the  medical  litera- 
ture, especially  that  of  France  and  Italy,  the  re- 
mainder of  this  article  will  be  devoted  to  brief  con- 
sideration of  the  forms  of  organotherapy  first  men- 
tioned the  use_of  the  extracts  of  spleen,  pancreas, 
liver,  and  duodenum. 

Practically  every  form  of  organotherapy  that  is 
recommended  in  tuberculosis  is  useful  only  as  it 
influences  nutrition,  and  this  is  essentially  true  of 
the  use  of  splenic  extract.     In  an  exhaustive  paper 


242  THE  INTERNAL  SECRETIONS 

on  the  subject,  (7)  the  writer  has  gathered  together 
some  information  regarding  the  fundamental  func- 
tions of  the  splenic  hormone,  and  concludes  that 
the  value  of  splenic  extract  in  practical  therapeu- 
tics may  depend  on  the  occurrence  of  a  hormone  or 
hormones  which  are  concerned  in  the  defenses  of 
the  blood  in  tryptic  and  intestinal  digestion  in  the 
reparative  processes,  and  in  certain  specific  func- 
tions on  the  part  of  the  spleen  itself.  Bayle,  of 
Cannes,  has  obtained  results  which  he  regards  as 
almost  of  a  specific  nature,  and  in  his  paper,  read 
before  the  last  International  Congress  at  Rome,  (8) 
he  concludes: 

"I  feel  authorized  by  my  results  to  call  splenic 
opotherapy  a  specific  treatment  for  tuberculosis.  It 
is  a  specific  from  the  therapeutic  viewpoint,  because 
it  modifies  the  soil,  rendering  it  less  suitable  as  a 
medium  for  the  culture  of  the  bacillus  of  Koch.  It 
is  a  specific  from  the  practical  viewpoint  because  it 
manifests  all  the  function  and  rapidity  of  action  of 
a  specific  medication.  Employed  in  convalescents 
it  prevents  tuberculosis  by  increasing  the  mineral 
content  of  the  tissue  (en  remineralisant  le  terrain). 
Employed  in  confirmed  cases  of  tuberculosis  it 
cures  them."  Bayle  has  recently  given  a  very  con- 
cise resume  and  bibliography  of  his  entire  work  on 
this  subject.  (9) 

Schroder,  (10,  11)  Superintendent  of  the  Neuen 
Heilanstalt  fur  Lungenkrankheit,  Schomberg, 
along  with  his  colleagues  there,  has  made  an  ex- 


IN  PRACTICAL  MEDICINE  243 

tensive  series  of  experiments  on  puppies  and  guinea- 
pigs,  and  concludes  that  the  administration  of 
spleen  extract  exercises  a  powerful  influence  against 
the  progress  of  inoculation  tuberculosis  in  these 
animals.  "The  minimizing  effect  of  the  spleen  ex- 
tract was  obvious,  insuring  a  longer  duration  of  life 
and  milder  lesions  in  the  animals  treated,  as  com- 
pared with  the  control  animals." 

Van  Stockum,  (12)  of  Amsterdam,  has  carried 
out  a  series  of  interesting  tests  in  the  treatment  of 
tuberculosis  with  extract  of  spleen  previously  ex- 
posed to  the  X-rays.  His  report  on  3,000  cases  so 
treated  is  convincing  evidence  that  the  use  of  this 
preparation  is  followed,  especially  in  the  surgical 
forms,  by  an  early  betterment.  He  also  lays  stress 
on  the  harmlessness  of  this  method.  In  a  recent 
editorial  (13)  appears  a  statement  which  deserves 
emphasis:  "The  subject  is  certainly  one  that  should 
not  be  lost  sight  of,  and  practitioners  may  well  re- 
member that  advantage  may  accrue  from  the  use  of 
splenic  substance  as  an  adjuvant  at  any  rate." 

Tuberculous  patients  are  invariably  sufferers 
from  toxemia,  not  only  the  specific  toxemia,  but 
also  that  due  to  stagnant  digestive  functions  and 
deficient  detoxicating  power.  We  know  that  the 
successful  use  of  various  liver  extracts  for  a  num- 
ber of  years  definitely  has  proved  that  they  have  a 
noticeable  detoxicating  power,  (14)  due  doubtless 
to  the  fact  that  the  internal  secretion  of  the  liver 
has  this  property.     This  is  probably  the  cause  of 


244  THE  INTERNAL  SECRETIONS 

much  of  the  good  that  has  resulted  from  the  use 
of  this  class  of  preparations.  Lemoine  and  Gerard 
(15)  have  brought  forward  a  petroleum  extract  of 
bile  called  "paratoxine,"  which  is  said  to  be  useful 
in  tuberculosis,  chiefly  on  account  of  its  antitoxic 
action. 

In  studying  this  subject,  and  applying  it  in  their 
extensive  clinical  work  in  Paris,  Gilbert  and  Car- 
not  (16,  17)  found  that  liver  extract  possessed  an 
antihemorrhagic  influence,  and  they  used  it  in  the 
treatment  of  hemoptysis,  especially  in  tuberculosis, 
with  very  encouraging  results.  In  cases  where  tu- 
berculosis is  associated  with  hepatic  enlargement 
and  derangement  this  form  of  organotherapy  con- 
fers great  benefit.  H.  Parmentier  (18)  reports  that 
liver  extracts  have  a  generally  good  influence  in 
tuberculosis,  causing  an  increase  in  weight  as  well 
as  a  decrease  in  the  night  sweats  and  number  of 
bacilli  in  the  sputum.  His  experiences  confirm  those 
of  Gilbert  and  Carnot,  which  proved  the  value  of 
liver  preparations  in  hemoptysis. 

It  has  been  frequently  suggested  that  the  thera- 
peutic value  of  codliver  oil  is  due  in  considerable 
part,  not  to  the  contained  fat,  but  to  a  certain  inter- 
nal secretion  of  the  liver  of  the  cod.  This  may  act 
directly,  or,  more  likely,  according  to  Leonard  Wil- 
liams, (19)  by  stimulating  one  of  the  normal  in- 
ternal secretory  glands,  the  secretion  of  the  one  so 
stimulated  being  inimical  to  the  development  of 
the  tubercle  bacillus.     It  is  a  significant  fact,  he 


IN  PRACTICAL  MEDICINE  245 

adds,  that  the  darker  and  more  crude  the  codliver 
oil  the  more  efficacious  it  is. 

The  pancreas  undoubtedly  plays  an  important 
part  in  defending  the  body  against  infection.  In 
proof  of  this  one  has  only  to  remember  the  fre- 
quency with  which  diabetics  suffer  from  boils  and 
local  infective  processes,  and  the  remarkably  high 
percentage  of  diabetics  that  suffer  and  die  from 
concomitant  tuberculosis.  This  leads  one  to  believe 
that  the  pancreas,  in  addition  to  its  known  func- 
tions, plays  an  important  part  in  regulating  resist- 
ance to  infection.  Brieger  (20)  has  shown  that 
pancreatin  lowers  the  abnormally  high  antitryptic 
index  of  the  blood  in  tuberculosis,  and  predicts  that 
eventually  treatment  will  be  on  the  lines  of  a  com- 
bination of  pancreatin  and  tuberculin.  Strubell  (21) 
has  made  the  definite  statement  that  pancreatin 
administered  per  os  increases  the  opsonic  index  to 
the  staphylococcus.  This  may  explain  some  of  the 
encouraging  results  obtained  from  spleno-pancre- 
atic-opotherapy  in  tuberculosis,  and  also  the  bene- 
fit to  the  diabetic  which  often  follows  pancreatic 
therapy.  Referring  to  this,  the  editor  of  the  Medi- 
cal Record  (22)  says :  "The  future  may  witness  the 
routine  use  of  pancreatin  in  tuberculosis  .  .  .  and 
in  many  chronic  affections  with  lowered  opsonic 
index." 

Digestion  is  almost  invariably  poor  in  tubercu- 
losis, and,  unfortunately,  in  no  class  of  disease  is 
a  vigorous  digestion  more  necessary.  The  tendency 


246  THE  INTERNAL  SECRETIONS 

to  push  the  feeding  of  the  consumptive  often  over- 
taxes digestion,  and  where  hyperalimentation  is 
necessary,  or  where  decreased  digestive  capacity 
has  already  made  itself  manifest,  secretin  is  a  most 
reasonable  and  useful  remedy. 

As  originally  shown  by  Bayliss  and  Starling, 
secretin  is  a  specific  chemical  activator  of  pancre- 
atic function,  produced  in  the  duodenal  walls.  Se- 
cretin actually  combines  with  the  precursors  of  the 
pancreatic  digestants  and  is  used  up  in  their  forma- 
tion. Other  investigators  have  shown  that  this  in- 
fluence is  not  confined  to  the  pancreas,  but  that 
secretin  stimulates  both  the  peptic  and  the  oxyntic 
glands  of  the  stomach,  as  well  as  those  glands 
which  produce  the  succus  entericus,  and  some 
French  investigators  pointed  out  that  secretin  also 
stimulates  the  liver.  Whether  the  influence  of 
secretin  is  or  is  not  as  widespread  as  has  been  stated 
above,  there  can  be  no  doubt  that  it  has  a  salutary 
influence  upon  digestion,  an  influence  nowhere 
more  essential  than  in  the  treatment  of  tubercu- 
losis. Boardman  Reed  draws  attention  to  the  or- 
ganic derivatives  as  valuable  factors  in  the  treat- 
ment of  indigestion,  and  gives  his  experiences  (23) 
with  a  preparation  called  "secretogen,"  which  con- 
tains gastric  and  pancreatic  secretins  and  entero- 
kinase,  with  0.5  per  cent.  HC1.  It  has  proved  in 
a  number  of  cases  to  be  much  more  effective  than 
the  usual  pepsin-HCl  combinations,  rapidly  bring- 
ing the  stomach  up  to  normal,  and  improving  the 


IN  PRACTICAL  MEDICINE  247 

intestinal  digestion  and  assimilation.  The  author 
gives  the  result  of  gastric  analysis  made  in  one  of 
the  cases,  in  which  secretogen  was  suspended  for 
a  month.  The  proportions  of  both  free  and  com- 
bined HC1  were  found  to  be  still  a  little  above  nor- 
mal, though  before  the  remedy  was  taken  there  had 
been  no  free  HC1  at  all,  and  the  proportions  of  both 
combined  HC1  and  total  acidity  were  below  normal. 

The  importance  of  hormones  in  the  treatment  of 
disease  is  daily  being  more  fully  recognized,  and 
there  is  little  doubt  that  before  long  their  value  as 
an  adjunct  in  the  treatment  of  tuberculosis  will  be 
generally  accepted.  The  results  already  published 
admit  of  no  doubt,  and  are  sufficient  at  least  to  dis- 
arm skepticism.  We  have  not  found  a  panacea  for 
tuberculosis,  nor  are  we  likely  to  find  one  soon;  but 
it  can  not  be  gainsaid  that  the  control  of  the  body 
functions  as  a  whole — and  especially  that  control 
aimed  at  in  an  attempt  to  regulate  the  hormone 
balance — will  be  eventually  a  very  important  factor 
in  the  successful  treatment  of  tuberculosis.  We 
shall  do  well  to  bear  this  in  mind,  not  forgetting 
that  "an  attitude  of  obstinate  unreceptive  skepti- 
cism leads  only  to  stagnation  and  death,  and  has 
certainly  no  place  in  an  atmosphere  where  men  are 
striving  to  unravel  difficult  and  elusive  prob- 
lems." (24) 

The  successful  therapist  owes  his  position  to  a 
thorough  attention  to  detail,  no  less  than  to  his  ap- 
preciation   of    probabilities,    both    diagnostic    and 


248  THE  INTERNAL  SECRETIONS 

therapeutic;  and  if  the  possibilities  of  hormone 
therapy  materialize,  as  they  bid  fair  to  do,  there  is 
every  hope  that  the  prevention  and  cure  of  the 
great  white  plague  eventually  may  become  an  ac- 
complished fact. 


Some  years  have  elapsed  since  the  foregoing 
pages  were  written.  On  reading  them  over  I  am 
reminded  of  some  comment  which  I  heard  in  Lon- 
don some  months  after  this  paper  first  appeared  in 
print:  Organotherapy  is  no  more  efficacious  in 
the  cure  of  tuberculosis  than  any  other  of  the  hun- 
dred and  one  therapeutic  offerings. 

Of  course  this  has  more  truth  in  it  than  fiction 
and  it  may  be  well  to  state  unequivocally  that  none 
of  the  measures  outlined  are  ''cures" — the  chapter 
heading  calls  them  "adjuncts." 

However,  of  one  thing  I  am  convinced  and  that 
is  that  pancreatin  is  indeed  a  valuable  remedy  in 
tuberculosis,  and  that  it  acts  in  two  separate  and 
distinct  ways.  Besides  its  beneficent  effects  upon 
digestion,  pancreatin  seems  to  antagonize  excessive 
adrenal  activity,  and  it  is  now  believed  by  several 
prominent  investigators  that  the  toxemia  of  tuber- 
culosis irritates  the  adrenals  quite  considerably  and 
this  hyperadrenia  is  responsible  for  several  of  the 
sympathetic  symptoms  such  as  dryness  of  the 
mouth,  irritable  heart,  digestive  crises  and  some  of 
the  sympathetic  nervous  derangement  not  uncom- 
mon in  the  tuberculous. 


IN  PRACTICAL  MEDICINE  249 

Whether  or  no  we  use  organotherapy  in  treating 
tuberculosis,  we  must  at  least  realize  more  than  we 
have  done  that  the  tuberculous  patient  has  an  endo- 
crine system  which  is  very  likely  to  be  affected, 
early  in  the  course  of  the  disease,  and  that  if  this 
is  true,  and  how  can  it  but  be,  the  endocrine  phase 
of  tuberculosis  is  worth  studying  in  the  light  of  our 
present  knowledge  of  the  importance  and  all-em- 
bracing effects  of  the  endocrine  principles  in  health 
and  disease. 

REFERENCES 

1.  See  American  Medicine,  New  York,  1913,  xix,  1,  5. 

2.  Brunet,  F. :  "Le  Sue  Pulmonaire :  Effets  Physio- 
logiques  et  Therapeutiques,"  Bull.  Med.,  Paris,  1896,  x, 
1239;  ibid.,  C.  R.  Soc.  Biol.,  Paris,  1897,  10,  iv,  24. 

3.  Grande,  E. :  "II  Polmone  un  Opoterapia,"  Rif orma 
Med.,  Naples,  1897,  xiii,  391. 

4.  Lorand,  A.:  "Old  Age  Deferred,"  1911,  chap, 
xxxvii,  p.  313. 

5.  Schafer,  E.  A. :  "The  Nature,  Origin,  and  Main- 
tenance of  Life,"  Lancet,  London,  1912,  ii,  675. 

6.  Lereboullet,  P. :  "Les  Opotherapies  dans  la  Tu- 
berculose,"  Paris  Medical,  1912,  51,  586. 

7.  Harrower,  H.  R. :  "Therapeutic  Action  of  Splenic 
Extract  in  Tuberculosis,"  Lancet,  London,  1913,  i,  524. 

8.  Bayle,  C. :  "L'Opotherapie  Splenique,"  Trans.  Int. 
Tuber.  Congr.,  Rome,  1912. 

9.  Bayle,  C. :  "Splenic  Opotherapy  in  Tuberculosis," 
Prescriber,  Edinburgh,  1913,  vii,  106. 

10.  Schroder,  G. :  "Uber  die  Rolle  der  Milz  als 
Schutzorgan  gegen  Tuberkulose  Infektion"  (I.  Teil),  Beitr. 
z.  Kl.  d.  Tuberkulose,  Wurzburg,  1909,  xii,  323. 

11.  Schroder,  Kaufmann,  and  Kogel:  Ibid.  (II.  Teil), 
Beitr.  z.  Kl.  d.  Tuberkulose,  Wurzburg,  1912,  xxiii,  1. 

12.  Van  Stockum,  W.  J. :    "Die  Therapeutische  Wirk- 


250  THE  INTERNAL  SECRETIONS 

ung  der   mit   Rontgen-Strahlen   Vorbehandelten   Milz   bei 
Tuberkulose,"  Wien.  Kl.  Wochenschr.,  1912,  xxv,  1857. 

13.  Editorial :  "The  Therapeutic  Action  of  Splenic 
Extract,"  Univ.  Med.  Record,  London,  1913,  iii,  326. 

14.  For  further  information,  see  "Opotherapie,"  P. 
Carnot,  1910,  p.  479;  "La  Pratique  de  l'Opotherapie,"  L. 
Hallion,  1911,  p.  22;  "Les  Produits  Biologiques  Medicin- 
aux,"  Byla  and  Delaunay,  1912,  p.  302. 

15.  Gerard,  E.,  and  Lemoine,  G. :  "Sur  la  Composi- 
tion de  l'Extrait  Ethere  (Lipoide)  de  la  Bile,"  Bull,  et 
Mem.  Soc.  Med.  d'Hop.  de  Paris,  1909,  3,  xxviii,  935.  See 
also  Nord  Med.,  Lille,  1909,  xvi,  121,  241,  253;  ibid.,  1910, 
xvii,  129;  Rev.  Mod.  de  Med.  et  de  Chir.,  Paris,  1910,  viii, 
165 ;  Med.  Moderne,  Paris,  1910,  xxxi,  93. 

16.  Gilbert,  A.,  and  Carnot,  P. :  "Note  Preliminaire 
sur  l'Opotherapie  Hepatique,"  C.  R.  Soc.  Biol.,  Paris  1896, 
10,  iii,  934;  ibid.,  "De  l'Opotherapie  Hepatique  dans  les 
Hemorragies,"  C.  R.  Soc.  Biol.,  Paris,  1897,  10,  iv,  445. 

17.  Carnot,  P. :  "L'Hemostase  par  Opotherapie  He- 
patique," Paris  Medical,  1911-12,  484. 

18.  Parmentier,  H. :  "Traitement  de  la  Tuberculose 
Pulmonaire  par  les  Extraits  Hepatiques  Totaux,"  Bull.  Gen. 
de  Ther.,  Paris,  1911,  clxi,  218. 

19.  Williams,  Leonard:  "The  Therapeutic  Promise 
of  the  Internal  Secretions,"  Practitioner,  London,  1911, 
lxxxviii,  605. 

20.  Brieger,  L. :  "Kombinationstherapie  bei  Pernizi- 
oser  Anamie,"  Deut.  Med.  Wochenschr.,  Berlin,  1912, 
xxxviii,  ii,  2154. 

21.  Strubell,  A.:  "Der  Einfluss  der  Hormone  auf  den 
Opsonischen  Index,"  Berl.  Kl.  Wochenschr.,  1912,  xlix,  2350. 

22.  Editorial :  "New  Aspects  of  Pancreatic  Organo- 
therapy," Medical  Record,  New  York,  1913,  lxxiii,  205. 

23.  Boardman  Reed :  "Organic  Derivatives  in  Indi- 
gestion," Amer.  Jour.  Gastro-Enterol.,  October,  1912  (abs. 
in  Prescriber,  Edinburgh,  1913,  vii,  147). 

24.  Williams,  L. :  "The  Quickening  Spirit,"  Brit.  Med. 
Journ.,  1910,  ii,  928. 


INDEX 


Acidosis  in  Rickets 223 

Adenoids     152,  218 

Adrenal    Asthenia    95 

—  Cortex   in   Cancer 182 

— 'Depletion     14 

—  Stigmata  in  Children 158 

Adrenals    in    Epilepsy 23 

—  in   General   Practice 76 

— ■  Relation  to  Neurasthenia  67 
Adrenalin,     Oral     Adminis- 
tration      229 

—  Analgesic    Effects  230 

—  in  Children's  Diseases.... 234 

—  in    Nephritis    235 

—  in   Oto-Rhinology   217 

—  in    Spotted   Fever 234 

—  in   War    Medicine 68 

—  Instillation  Test  19  3 

Adrenin  78 

Alkalies  in  Hyperthyroid- 
ism     188 

Alkalinity  of  Blood 37 

Altruistic  Cell  Activities 

46,  167 

Amenorrhea   107 

—  Pituitary  in  170 

Analgesic  Effects  of  Ad- 
renalin  230 

Anoci-association   14,  63,  77 

Anterior    Pituitary    in    Hy- 
perthyroidism      195 

Principle     156 

Asthenia    91 

—  Adrenal    78 

—  Endocrine    26,  91 

—  Thyroid    94 

Asthenopia    219 

Blazek  Twins  202 

Blindness,    Pituitary   Origin   59 

Cancer — Chemical    Cause....   20 

—  Fundamentals  of  Causa- 

tion      172 

—  Grafts,  Effects  of  Castra- 

tion   on    175 

—  Organotherapy     in.. ..57,  163 


—  Uterine,  Mammary  Ther- 

apy      171 

Calcium  Lactate  with  Para- 
thyroid       23 

—  Lactophosphate     222 

Cannon's    findings    79 

Cellular  Infiltration  144 

Cerebral  Edema  23 

Children,      Defective     from 

Endocrine   Standpoint 148 

—  Thyroid  Dosage  in 35,41 

—  Thyroid  Stigmata  in  34 

Chromaffin  Hormone  ....78,  233 
Chronic      Disease,     Internal 

Secretions    in  6 

Organotherapy    in 163 

Cod    Liver    Oil 244 

in  Rickets  225 

Constipation,    Thyroid    Ori- 
gin  of   i4i 

Constitution,   Jerry   Built....   36 
Corpus  Luteum  (Lutein)  in 

Neurasthenia    108 

in  Gynecology  ....111,  120 

in  Obesity  40 

with   Thyroid   40,107 

Cretinism    149 

Deafness   213 

Defective  Children  ".."l48 

Organotherapy  56 

Demineralization    180 

Dermographia     158 

—  in   Neurasthenia   65 

Diabetes  Mellitus  25 

Diagnostic    Use  of    Thyroid 

Extract    145 

Didymin 121 

Diet   in   Hyperthyroidism.. ..191 

—  in   Rickets  226 

Dizziness  213 

Dyscrinism    62,  67 

—  Adrenal   Origin   81 

—  in   Children   149 

—  in   Sex   Disabilities 118 

Dysgenitalism  119 

(251) 


252 


THE  INTERNAL  SECRETIONS 


Dysmenorrhea,  Adrenal  Or- 
igin of  87 

—  at  Menopause   ..109 

—  Pituitary  in  170 

Therapy    107 

—  Thyroid    Origin  of 34 

Dysovarism     86 

Dyspituitarism  in    Wom.en.-109 
Dystrophia-adiposo         geni- 
talis      96, 116 

Edema  of  Brain 137 

—  Thyroid    144 

Ehrmann's  Test  80 

Emotions,  Influence  on  Ad- 
renals        76 

—  Cause   of    Hyperthyroid- 

ism      81, 190 

Endocrine  Stimulation  50 

—  Disease,  Syphilis  a    Fac- 

tor in  12,  27,  47,  49 

Endocrinasthenia     26,  91 

Epilepsy    22 

—  Adrenal   Factor   in 83 

—  Pancreatin    in    84 

—  Thyroid  Gland  in 136 

"Epinephrine"    235 

Eye    Findings    in    Pituitary 

Disorder    220 

in   Thyroid   Disorder. .219 

Fibroids    204,  207 

Focal    Infection,    Effect    on 

Thyroid     190 

Froehlich's  Syndrome  96 

Functional  Disorders,  Rela- 
tion of  Endocrine  Glands   16 

Gonad   Extracts   120 

—  Insufficiency     98,116 

Green    Bone  223 

Hallion's    Law  3,  50 

Heart  Disease,  Adrenal  Ex- 
tract in  236 

—  Failure,   Treatment  of... .232 
Hemianopsia,   Bitemporal. ...219 
Hepatic  Extract  in  Hemop- 
tysis      244 

Hereditary    Thyroid    Insta- 
bility   141 

Homostimulation   3 


Hormone  Balance  ....20,  46,  240 

Hormone  Therapy  255 

Hormotone    53,  71,  99,  110,  122 
Hyperadrenia   84 

—  in  Tuberculosis  248 

—  Symptoms  of  248 

Hyperovarism     204 

Hyperthyroidism    185 

—  Diet  in  191 

—  Emotional   Origin   ....81,190 
Hypoadrenia 14 

—  Acute   86 

—  Influence  on    Gonads 117 

—  in    Neurasthenia  88 

—  Symptoms  of  63 

—  Terminal    85 

Hypocrinism     105 

—  See     Pluriglandular     In- 

sufficiency. 

—  in  Tuberculosis  239 

Hypopituitarism  9  6 

—  Gonads   in   116 

Hypothyroidism   106 

—  See  Thyroid  Insufficiency. 

—  in  Cancer  176 

—  in  Rheumatism  129 

—  Symptoms    33 

Hypoplasia    150 

Idiopathic  Epilepsy  136 

Impotence     117,  120 

Indigestion  of  Adrenal  Ori- 
gin        38 

Infantilism    150 

—  Pituitary    96,  157 

Infiltration,   Thyroid   144 

Intestinal  Antisepsis   187 

—  Irritation     (Thyroid)    ....189 

—  Stasis   137 

Kephalin     217 

Loewi's  Test  193 

Lymphatic   Gland    Extract..217 
Lymphocytosis    154 

Malaria,  Adrenal  Factor  in   85 
Mamma   an   Internal   Secre- 
tory  Gland   196 

—  Hormone    198 

Mammary   Evolution   200 

—  Extract     204 


IN  PRACTICAL  MEDICINE 


253 


Dosage  of  211 

in    Menorrhagia. .105,  206 

in  Uterine  Cancer 171 

Menopausal     Neurasthenia.. 10  8 
Menorrhagia,    Mammary 

Therapy  in  r.105,  206 

Menstrual   Neurasthenia 104 

Metabolism,   Thyroid    Influ- 
ence on  132 

Mucous  Colitis   187 

Myasthenia  Gravis  98 

Nasal  Disorders,  Endocrine 
Glands   in   212 

—  Obstruction    139 

Nephritis,    Adrenalin    in 235 

Neurasthenia    24,  53 

—  Adrenal  Symptoms  in  66,  87 

—  and  Shell  Shock 62 

—  in  Women   100 

—  Pituitary   Origin   97 

Nocturnal   Enuresis  33,  152 

Nutrition,   Effects    of    Thy- 
roid  on   34 

Obesity    40,  109 

Optic  Atrophy,   Primary 220 

Organotherapy,  Forms  of.—      3 
Oto-Rhinology,  Internal  Se- 
cretions  in   212 

Ovarian  Neurasthenia  104 

—  Rheumatism    132 

Ovaries,  Influence  on  Mam- 
mae   201 

Pain  Effects  on  Adrenals... .   14 

Palate,   High    Arched 153 

Pancreas,  in  Diabetes 25 

—  Extract   in    Cancer 182 

Pancreatin  in  Epilepsy 84 

—  in   Hyperthyroidism   193 

—  in  Tuberculosis  245,248 

Paralysis      Agitans,      Impo- 
tence  in    118 

Parathyroid    Disease,     Gon- 
ads in  118 

Parathyroids   in  Epilepsy....   23 

Pedology  158 

Pineal,    Influence   upon   Sex 
Development     118 

—  Origin  of  Asthenia 98 


Pituitary  and  Thyroid  Ther- 
apy       58 

i — Asthenia     96 

—  Disease,  Eye  Findings. ...219 
Successful    Treatment   58 

—  Extract   in   Epilepsy.. 23 

in     Hyperthyroidism..!  8  6 

in   Impotence   120 

in    Shock,    etc 69 

—  Infantilism     157 

—  Relation  to   Growth 156 

Pituitrin,  Heart  Value  of....      9 

—  to    Forestall    Bleeding.. ..217 
Pluriglandular  Insuffi- 
ciency     11,  43,  168 

—  Therapy   ..52,  58,  70,  74,  224 
Prophylaxis  of  Develop- 
mental Disorders  159 

Protan     in     Thyroid     Diar- 
rhea      189 

Psychic  Causes  of  Shock....   64 
Pyorrhea    in    Hyperthyroid- 
ism     189 

—  Relation  to   Goiter 216 

Raynaud's    Disease  140 

Rheumatism  ....18,  21,  123,  131 
Rickets    35,  155,  222 

—  Cod  Liver  Oil  in 225 

—  Thymus  Atrophy  in 224 

Roberts-Hawley    Lymph 

75,  99,  121 

Scaphoid  Scapula  152 

Secretin     246 

—  in    Cancer   177 

Sellar  Radiography  156 

Senility,  Organotherapy  in..   55 

—  Relation  of  Cancer 183 

Sequarine   121 

Sex  Glands,  see  Gonads. 

—  Disabilities     114 

Sexual  Neurasthenia   107 

Shell   Shock   62 

Sodium    Bicarbonate    ..188,  223 

—  Cacodylate  with  Thyroid   39 

—  Citrate   in    Rickets 223 

"Soldier's  Heart"  66 

Spleen  Extract  181,  242 

Spotted  Fever,  Adrenalin  in  234 

Stasis,   Intestinal   137 

Status  Thymo-lymphaticus.-154 


254 


THE  INTERNAL  SECRETIONS 


Sugar  Feeding  in  Cancer...-182 

Sympathetico-tonus    78 

Suprarenals,  see  Adrenals. 
Syphilis     27 

—  and    Endocrine    Disorder  12 

—  in     Pluriglandular     Dis- 

ease     47,  49 

Tabloid    Mixed    Glands 

99,  122,  159 

Testicles,  Influence  on  Can- 
cer Grafts  175 

Testicular   Therapy   120 

Tethelin    156 

Thromboplastin    217 

Thymus  Absence   155 

—  Asthenia    97 

—  Atrophy   in   Rickets 224 

—  Enlargement    153 

—  Extract     181 

—  Relation  to  Rheumatism  134 

—  Influence   on    Gonads IIS 

Thyroid   Active  Principle....   10 

—  Amenorrhea     107 

—  Asthenia    94 

—  Disorders,  Minor  11 

Symptoms     38 

—  Extract,   Diagnostic  Val- 

ue of  145 


Thyroid      Extract,     Dosage 

of     10,  32,  35,  40 

in     Epilepsy   143 

in    Rickets 224 

—  Heart   66 

—  Influence   on    Gonads 115 

—  Insufficiency,    Minor    ..11,30 

—  in    Rheumatism..22,  127,131 

—  Preparations,    Variations 

of   41 

—  Stigmata  in  Children 34 

Tonsils,  Relation  to  Goiter  215 

—  Disease  in   Children 152 

Transmission    of   Endocrine 

Disorders    160 

Tuberculosis  18,  25 

—  Organotherapy  in  237 

—  Pancreatin   in   245 

Uterine  Hemorrhage  

170,  171,  204 

Uterus,   Cancer  of 171 

—  Functional  Disorders   .... 

87,  104,   107,109,170,  206 

Vegetable    Consomme..l92,  227 
Virilism     117 

Weight,    Loss    of. 65 


By  the  Same  Author 

Practical  Hormone  Therapy 

A  Manual  of  Organotherapy  for  General  Practitioners 

Foreword  by  Prof.  Dr.  Artur  Biedl 
A  N  intensely  interesting  book  on  the  therapeutics  of  the 
**•  internal  secretory  glands,  which  covers  every  phase 
of  the  subject  in  a  clear  and  interesting  manner.  It  is  not 
a  book  on  the  internal  secretory  glands,  but  on  the  thera- 
peutics which  the  increasing  knowledge  of  these  organs 
has  made  possible.     It  contains  : 

An  extensive  index — 26  columns,  37  chapters  and  508  pages. 
A  helpful  glossary  including  94  terms. 
An  organotherapy  dose-table  with  165  indications. 
A  useful  list  of  32  books  on  the  internal  secretions. 
An  interesting  chart  of  the  relations  of  the  ductless  glands. 

Medical  Record  (New  York)  :  Southern     Medical     Journal 

"In  this,  the  latest  contribu-  (Mobile):  "For  the  past  few 
tion  to  the  subject  of  the  inter- 
nal secretions  and  of  their  val- 
ue as  medicinal  agents,  the  au- 
thor displays  a  comprehensive 
knowledge  of  the  extensive  lit- 
erature on  this  subject.  In- 
deed, with  the  reference  in  the 
text  and  the  bibliographic  list 
at  the  end  of  each  chapter 
there  is  presented  a  digest  of 
almost  everything  that  has 
been    written    on    this    subject. 

New  York  Medical  Journal: 

"Harrower's  book  is  very 
satisfactory  and  shows  evidence 
of  considerable  research  in  the 
literature  of  the  many  subjects 
treated." 

The  Medical  Press  (Dublin) : 
"The  author  has  given  us  an 
extensive  treatise  on  organo- 
therapy. He  tells  all  that  is 
known.  .  .  .  works  of  this 
kind  which  synoptize  the  re- 
sults obtained  by  countless  sci- 
entific laborers  are  of  much 
service." 

Price  $4.50,  prepaid  $4.70. 

Obtainable  from  the  Publisher  of  this  book  or  from  the 

Author  direct — on  approval  if  desired. 


years  there  has  been  almost  un- 
paralleled progress  in  this 
branch  of  medicine.  This  book 
is  particularly  interesting  in 
that  it  is  the  only  one  of  its 
kind  in  English;  it  opens  out 
before  us  the  many  possibili- 
ties of  organotherapy  and  in- 
spires interest  in  the  various 
and  necessary  metabolic  chang- 
es wrought  by  the  hormones." 

Buffalo  Medical  Journal: 
"We  feel  it  is  not  too  much  to 
assert  that  this  book  marks  an 
epoch  in  medical  history.  It 
systematizes  and  collates  all 
the  fundamental  details  and  to 
a  considerable  degree  affords 
work  for  future  investigation." 

Boston  Medical  and  Surgical 
Journal:  "This  work  places  in 
the  hands  of  English  readers  a 
valuable  compendium  on  a  sub- 
ject hitherto  treated  almost 
solely  by  continental  European 
writers." 


ENDOCRINOLOGY: 

The  Bulletin  of  the  Association  for  the  Study  of  the 
Internal  Secretions 

This  new  journal  was  originated  by  Doctor  Harrower, 
and  he  is  at  this  writing  its  Managing  Editor. 

It  is  published  quarterly  and  the  first  issue  was  pub- 
lished in  1917. 

It  contains : 

Editorial  articles  by  well-known  authorities. 

Original  communications,  each  accompanied  by  the  comment 
of  several,  thus  broadening  their  value  to  the  reader. 

A  review  department  containing  numerous  abstracts  of  cur- 
rent literature  on  the  internal  secretions,  conveniently  divided 
into  four  sections — General,  Experimental,  Clinical  and  Thera- 
peutic. 

A  cross-index  of  subjects  and  authors  in  each  journal.  This 
is  a  decidedly  valuable  innovation  in  medical  journalism,  thus 
favoring  the  utmost  convenience  in  looking  up  current  literature. 

ENDOCRINOLOGY  is  an  up-to-date  resume  of  the 
subject  and  is  but  a  part  of  the  advantages  of  member- 
ship in  this  Association.  The  Secretary,  Dr.  Emil  Goetsch, 
Johns  Hopkins  Hospital,  Baltimore,  Maryland,  will  be 
pleased  to  send  further  information  to  interested  physicians 
on  request. 


DATE  DUE 

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